Decision support tool for stroke patients

ABSTRACT

An automated system and method for assisting in decision making for the treatment of stroke patients is provided, and specifically for assisting a physician whether the patient should be administered a drug or transferred to another hospital to undergo an endovascular thrombectomy procedure. A variety of factors are input into the system with limited human intervention and a tool automatically determines the probability of whether the patient will have a better outcome if transferred or not. The factors include clinical factors, imaging factors and time to transfer factors. The tool includes processes for automatically determining several imaging factors, including the determination of clot length, collateral blood flow, the presence of forward blood flow within and around the clot, and the clot permeability. The tool has capability to continuously update the treatment protocol and other output results using current clinical, health system or other relevant information or feedback.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.62/086,077 filed Dec. 1, 2014 entitled SYSTEMS AND METHODS FOR ASSISTINGIN DECISION MAKING AND TRIAGING FOR ACUTE STROKE PATIENTS, which ishereby incorporated by reference.

FIELD

Embodiments described herein relate generally to stroke patients andtheir physicians or healthcare providers, and more specifically tosystems and methods to assist physicians or healthcare providers indecision making for patients who are experiencing or have experiencedacute ischemic stroke.

BACKGROUND

When a physician or healthcare provider initially suspects that apatient has had a stroke, the physician will undertake a number of stepsto verify the diagnosis. In initially diagnosing whether the patient hassuffered a hemorrhagic or an ischemic stroke, the physician may haveinitially completed brain imaging using an image scanner. This initialhigh level diagnosis is important in considering treatment options andin particular whether or not to administer thrombolytic drugs, which maybe referred to as a clot dissolving or busting drug. Until recently, thethrombolytic drug referred to as a pharmacological tissue plasminogenactivator (tPA) has been the only non-surgical standard of care fortreating patients with acute ischemic stroke. There are severaldifferent types of tPA which is a recombinant human protein. Alteplaseis the generic name of the marketed version of tPA that is used to treatstroke. As is known, tPA works by breaking up the thrombus or blood clotblocking blood flow to the brain that had caused the stroke. While thisnon-surgical treatment is highly effective in many scenarios, the drugmay not succeed in dissolving the thrombus when the thrombus itself iseither too large and/or the thrombus does not have the porosity toenable effective and timely penetration of the drug within the thrombus.In addition, tPA cannot be given to people who are taking blood thinnersor have had recent surgery or have another of several medicalcontraindications to thrombolytic therapy.

It is in this context that recent stroke trials have shown efficacy ofanother treatment, namely the use of various endovascular techniques andspecifically, the use of catheter systems to remove a thrombus fromwithin the brain arteries. Endovascular therapy is highly efficacious,however it entails a very high level of expertise from the surgicalteams as well as the supporting infrastructure. As such, it is limitedto a relatively small number of tertiary care hospitals across theworld.

As a result, given the generally resource intensive nature ofendovascular therapy and the required skill levels of the physicians,these procedures may generally only be available in a relatively lownumber of large hospitals.

Stroke, however, is a common disease with a wide range of severity. Thatis, minor strokes may require no treatment whereas non-fatal severestrokes can result in a wide range of outcomes for the patient and awide range of disabilities. As such, the ultimate outcome of the patientcan be affected by a number of factors.

Importantly, many stroke patients will be taken to hospitals near theircommunity where endovascular therapy is unavailable. Some of thesepatients may benefit from thrombolytic drugs (e.g. alteplase), whileothers may need to be transferred to a larger tertiary hospital in orderto benefit from endovascular therapy.

Decisions on whether to transfer patients need to be made quickly, asevery minute counts in cases where endovascular therapy is the preferredtreatment. That is, in a typical acute ischemic stroke case whereaffected areas of the brain are at risk of dying, every minute untilreperfusion the brain loses on average of 1.9 million neurons, 14billion synapses and 7.5 miles of myelinated fibers. On the other hand,in cases where affected areas of the brain are already irreversiblyinfarcted, decisions have to be appropriate and correct to avoidpatients being transferred to larger hospitals where endovasculartherapy is unlikely to produce a better outcome for the patient.

Currently, the expertise needed to make these triaging decisions isunavailable in community hospitals. As a result, physicians in thesecommunity hospitals may make decisions that result in significant costsin unnecessarily transferring patients to larger centers and incurringadditional diagnostic and treatment costs at these larger centers whenthe treatment outcome is unlikely to have been improved. On the otherhand valuable time may be lost in decision-making and other delays intransfer of patients at the community hospitals who may actually benefitfrom the transfer to a tertiary care hospital for endovascularthrombectomy.

SUMMARY

In an aspect of embodiments described herein, there is providedautomated decision support tools, systems and methods for determiningwhether a stroke patient should be transferred from a first hospital(i.e. a community hospital) to a second larger hospital (i.e. a tertiaryhospital) where endovascular therapy is available, or whether a strokepatient should be kept at the first hospital. An example system mayassist in determining if transfer is going to be beneficial or futile.In some embodiments, the system may do so by determining if thethrombolytic drug (administered at the community hospital) is going tobe successful in dissolving the thrombus or not and by determining theamount of brain that is already irreversibly infarcted or is likely tobe irreversibly infarcted in the time it takes for the transfer from thecommunity hospital to the tertiary hospital. The system may also takeinto account practical considerations, such as distance from thetertiary hospital, age of the patient (date or range, for example) andseverity of stroke symptoms, for example, to provide tangible outputresults in helping the physician make a transfer decision. The systemmay use efficient processing techniques to generate output results. Insome embodiments, input factors considered by the system for assisting aphysician's decision-making regarding stroke patients include thefundamental severity of the stroke, the specific treatment received aswell as determining estimates of various time components contributing tothe treatment including time passage from initial symptom onset tomobility of the patient for treatment, travel time to a care facility,initial diagnosis at the care facility, imaging time, additionaldiagnosis time of the extent and severity of the stroke, time toadministration of drugs and/or the initiation of endovascular therapy,and so on.

In another aspect, there is provided a method for a decision supporttool for evaluating a patient suffering from acute stroke.

The method may involve receiving patient clinical information andpatient brain scan electronic images at a processor; generating, at theprocessor, a patient brain imaging profile using the patient clinicalinformation and the brain scan electronic images, the imaging profileidentifying a quantity and eloquence of brain tissue that isirreversibly infarcted, an estimated rate or quantity of patient braintissue that become irreversibly infarcted at a future time, a thrombusmorphology associated with an estimate of a thrombus dissolving at thefuture time, and an estimated collateral blood flow; determining anestimated transport time to transfer the patient to a treatment facilityand an estimated treatment time for receiving reperfusion at thetreatment facility; dynamically determining, using the processor, apatient assessment profile by: processing the patient clinicalinformation, the patient brain imaging profile, the estimated transporttime, and the estimated treatment time to generate input data values;dynamically deriving weighting factors as an assessment of importance orrelevance of the input data values and assigning the weighting factorsto the input data values; deriving as output data values for the patientassessment profile using the input data values and the weightingfactors, the output data values being a probability of an experttreatment decision for transferring the patient to the treatmentfacility and providing the reperfusion at the treatment facility, and avisual representation of the thrombus morphology, the estimatedcollateral blood flow, and an estimated quantity of brain tissue thatwill likely become irreversibly infarcted after the estimated transporttime and/or the estimated treatment time; and outputting the output datavalues as clinical decision support information for triggering displayon a display device, for storing on a storage device, or fortransmission to another processor using a transmitter. The eloquence maydefine or reference how important the function of the brain tissue is.The method may involve determining collateral blood flow using one ormore T_(max) values as described herein to provide various visualrepresentations of the estimates. The processor may be configured withvarious threshold values for the probability of the expert treatmentdecision that may be physician or health care facility dependent, whereeach threshold value may trigger an action or predefined output result.For example, a probability of the expert treatment decision over 80% maytrigger a transport action.

In some embodiments, the method may involve determining that the patientis already at the treatment facility and updating the visualrepresentation with the estimated quantity of brain tissue that willlikely become irreversibly infarcted after the estimated treatment timefor receiving reperfusion.

In some embodiments, the method may involve determining or receiving apatient clinical data profile identifying an age or age range for thepatient and a stroke severity, the stroke severity defined on a scale ofmild, moderate and severe or based on physician heuristics, anddetermining the patient assessment profile using the patient clinicaldata profile as input to the system model.

In some embodiments, the method may involve determining the time elapsedsince the onset of stroke symptoms as an additional input data value forthe patient assessment profile.

In some embodiments, the method may involve determining the patient'spre-morbid status, general health and co-morbidities as an additionalinput data values for the patient assessment profile.

In some embodiments, the method may involve determining the patient'sadvanced directives as an additional input data values for the patientassessment profile.

In some embodiments, the method may involve determining currentmedications and/or medical history of patient that significantlyinfluence decision making as an additional input data value for thepatient assessment profile, including blood thinners and recent surgery.

In some embodiments, the method may involve providing an imaginginterface to connect to an imaging device to receive the brain scanimage files, the imaging device selected from the group consisting of ascanner, a picture archiving communication system network, and a cloudimage storage device.

In some embodiments, the method may involve determining the estimatedtransport time and the estimated treatment time comprises determining arequired treatment for the patient and identifying one or more availabletreatment facilities based on available treatment services andequipment, available treatment times, available transportation type andthe required treatment of the patient. The method may also involvedetermining other time estimates, such as the estimated transit time ofthe cerebral perfusion image or other types of images.

In some embodiments, the method may involve continuously updating thepatient assessment profile using a feedback loop based on additionalinput data values including configurations for the current physician andhealth system, additional available patient and health system data,changing configurations for the physician and health care facility,updates for the one or more weighting factors, control commands receivedfrom a display device displaying the visual representation.

In some embodiments, the method may involve constructing andcontinuously validating the patient assessment profile and the inputdata values using current and future clinical trial datasets.

In some embodiments, the method may involve constructing andcontinuously validating the patient assessment profile by receivingadditional data and results on adjuvant therapies includingneuro-protection and augmented thrombolytic techniques to changephysician and health system heuristics.

In some embodiments, the method may involve receiving threshold data fora health care provider to update and customize the patient assessmentprofile, the weighting factors, and the input data values for the healthcare provider, the health care data including number of treatmentcenters providing endovascular treatment, staff availability, and othercurrent health care metrics.

In some embodiments, the method may involve determining the patientassessment profile by determining a rate of brain tissue death usingcollateral assessment on various image scans, such as computedtomography (CT) angiography (CTA), CT Perfusion (CTP), Magneticresonance imaging (MRI) or a combination of thereof.

In some embodiments, the method may involve the likelihood of thethrombus dissolving within a specific future time as determined by oneor more techniques of measuring thrombus morphology such as a size ofthe thrombus, length of the thrombus, surface area of the thrombus,volume of the thrombus, and permeability to blood flow of the thrombus.

In some embodiments, the method may involve determining a likelihood ofthe thrombus dissolving with administration of a thrombolytic drug usingthe thrombus morphology and the collateral blood flow, the patienttreatment protocol indicating the likelihood of the thrombus dissolvingwith administration of the thrombolytic drug.

In some embodiments, the method may involve the output data values ofthe patient assessment profile to indicate a comparison between risks ofthe administration of a thrombolytic drug and risks of endovasculartreatment, the risks including a bleeding risk and other potentiallymajor risks associated with thrombolytic drug administration and atreatment risk of not being able to administer the endovasculartreatment or not successfully providing the endovascular treatment.

In some embodiments, the method may involve the collateral blood flow asdetermined using multi-phase CTA (mCTA), T₀ and T_(max) values.

In some embodiments, the method may involve the patient brain electronicimages as one or more imaging modalities selected from the groupconsisting of CT scan, multi-phase CTA, and CT perfusion, MRI, TransCranial Doppler (TCD), ultrasound (US), Electrical ImpedancePlethysmography (EIS) and other imaging modalities.

In some embodiments, the patient treatment protocol is selected from thegroup consisting of: transferring the patient to the treatment facilityfor treatment with endovascular therapy; transferring the patient to thetreatment facility for direct treatment without additional or repeatingbrain scans; retaining the patient at an initial treatment facility fortreatment with a thrombolytic drug; and retaining the patient at theinitial treatment facility.

In some embodiments, the method may involve receiving additionalpatient, clinical and imaging data for stroke patients; updating theinput data values using the additional patient, clinical and imagingdata for stroke patients; and updating patient treatment protocol usingmachine learning and the additional patient data, health system data,the updating by applying additional weighting factors to the updatedinput data values.

In some embodiments, the treatment protocol provides a visualrepresentation as a time-based a Computed Tomography Perfusion (CTP) mapinterface for display on the display device. The map interface mayreceive control commands and other feedback to re-generate or update thetreatment protocol based on the displayed visual representation.

In some embodiments, treatment protocol indicates one or more of anautomated prediction of thrombus lysability using the thrombusmorphology, an automated quantitation of collateral status on a CTP mapand on multi-phase CTA and an automated assessment of severehypoattenuation on non-contrast CT.

In another aspect there is provided a decision support computing tool.The tool may have an image interface to receive patient brain electronicimages. The tool may have a processor to: receive patient clinicalinformation; generate a patient brain imaging profile using the patientbrain scan electronic images and the patient clinical information, theimaging profile identifying a quantity and eloquence of brain tissuethat is irreversibly infarcted, an estimated rate or quantity of patientbrain tissue that will become irreversibly infarcted at a future time, athrombus morphology associated with an estimate of a thrombus dissolvingat the future time, and an estimated collateral blood flow; determine anestimated transport time to transfer the patient to a treatment facilityand an estimated treatment time for receiving reperfusion at thetreatment facility; and dynamically determine a patient assessmentprofile by: processing the patient clinical information, the patientbrain imaging profile, the estimated transport time, and the estimatedtreatment time to generate input data values; dynamically derivingweighting factors as an assessment of importance or relevance of theinput data values and assigning the weighting factors to the input datavalues; deriving output data values for the patient assessment profileusing the input data values and the weighting factors, the output datavalues being a probability of an expert treatment decision fortransferring the patient to the treatment facility and providing thereperfusion at the treatment facility, and a visual representation ofthe thrombus morphology, the estimated collateral blood flow, and anestimated quantity of brain tissue that will become irreversiblyinfarcted after the estimated transport time and/or the estimatedtreatment time. The tool may have a display device to display thepatient treatment protocol as clinical decision support informationincluding the visual representation. The tool may have a networkinterface to provide the output data values for transmission or storage.

In some embodiments, the processor determines that the patient isalready at the treatment facility and triggers a graphical update to thevisual representation with the estimated quantity of brain tissue thatwill likely become irreversibly infarcted after the estimated treatmenttime for receiving reperfusion.

In some embodiments, the processor determines or receives a patientclinical data profile identifying an age or age range for the patientand a stroke severity, the stroke severity defined on a scale of mild,moderate and severe or based on physician heuristics, and determine thepatient assessment profile using the patient clinical data profile.

In some embodiments, the processor receives or otherwise determines thetime elapsed since the onset of stroke symptoms for use as an additionalinput data values for the patient assessment profile.

In some embodiments, the processor utilizes the patient's pre-morbidstatus, general health and co-morbidities as an additional input datavalues for the patient assessment profile.

In some embodiments, the processor utilizes the patient's advanceddirectives as an additional input data values for the patient assessmentprofile.

In some embodiments, the processor utilizes current medications and/ormedical history of patient that significantly influence decision makingas an additional input data values for the patient assessment profile,including blood thinners and recent surgery.

In some embodiments, the processor provides an imaging interface toconnect to an imaging device to receive the brain scan image files, theimaging device selected from the group consisting of a scanner, apicture archiving communication system network, and a cloud imagestorage device.

In some embodiments, the processor determines the estimated transporttime and the estimated treatment time comprises determining a requiredtreatment for the patient and identifying one or more availabletreatment facilities based on available treatment services andequipment, available treatment times, available transportation type andthe required treatment of the patient.

In some embodiments, the processor continuously updates the patientassessment profile using a feedback loop based on additional input datavalues including configurations for the current physician and healthsystem, additional available patient and health system data, changesconfigurations for the physician and health care facility, updates theone or more weighting factors, and processes control commands receivedfrom a display device displaying the visual representation.

In some embodiments, the processor constructs and continuously validatesthe patient assessment profile and the input data values using currentand future clinical trial datasets.

In some embodiments, the processor constructs and continuously validatesthe patient assessment profile by receiving additional data and resultson adjuvant therapies including neuro-protection and augmentedthrombolytic techniques to change physician and health systemheuristics.

In some embodiments, the processor receives threshold data for a healthcare provider to update and customize the patient assessment profile,the weighting factors, and the input data values for the health careprovider, the health care data including number of treatment centersproviding endovascular treatment, staff availability, and other currenthealth care metrics.

In some embodiments, the processor determines the patient assessmentprofile further comprises determining a rate of brain tissue death usingcollateral assessment on CTA, CT Perfusion, MRI or a combination ofthereof.

In some embodiments, the processor determines the likelihood of thethrombus dissolving the over future time is determined by one or moretechniques of measuring thrombus morphology such as a size of thethrombus, length of the thrombus, surface area of the thrombus, volumeof the thrombus, and permeability to blood flow of the thrombus.

In some embodiments, the processor determines a likelihood of thethrombus dissolving with administration of a thrombolytic drug using thethrombus morphology and the collateral blood flow, the patient treatmentprotocol indicating the likelihood of the thrombus dissolving withadministration of the thrombolytic drug.

In some embodiments, the processor determines the output data values ofthe patient assessment profile that indicates a comparison between risksof the administration of a thrombolytic drug and risks of endovasculartreatment, the risks including a bleeding risk and other potentiallymajor risks associated with thrombolytic drug administration and atreatment risk of not being able to administer the endovasculartreatment or not successfully providing the endovascular treatment.

In some embodiments, the processor determines the collateral blood flowusing mCTA, T₀ and T_(max) values.

In some embodiments, the processor determines the patient brainelectronic images of one or more imaging modalities selected from thegroup consisting of CT scan, multi-phase CTA, and CT perfusion, MRI,TCD, EIS and other imaging modalities.

In some embodiments, the processor determines the patient treatmentprotocol selected from the group consisting of: transferring the patientto the treatment facility for treatment with endovascular therapy;transferring the patient to the treatment facility for direct treatmentwithout additional or repeating brain scans; retaining the patient at aninitial treatment facility for treatment with a thrombolytic drug; andretaining the patient at the initial treatment facility.

In some embodiments, the processor is configured to: receive additionalpatient, clinical and imaging data for stroke patients; update the inputdata values using the additional patient, clinical and imaging data forstroke patients; and update patient treatment protocol using machinelearning and the additional patient data, health system data, theupdating by applying additional weighting factors to the updated inputdata values.

In some embodiments, the processor determines the treatment protocol asthe visual representation on a time-based Computed Tomography Perfusion(CTP) map interface.

In some embodiments, the processor determines the treatment protocolindicates one or more of an automated prediction of thrombus lysabilityusing the thrombus morphology, an automated quantitation of collateralstatus on a CTP map and on multi-phase CTA and an automated assessmentof severe hypoattenuation on non-contrast CT.

In another aspect, there is provided an imaging system for evaluating apatient suffering from acute stroke. The imaging system receives patientbrain electronic images. The imaging system has a decision supportcomputing tool with a processor to: receive patient clinicalinformation; generate a patient brain imaging profile using the patientbrain scan electronic images and the patient clinical information, theimaging profile identifying a quantity and eloquence of brain tissuethat is irreversibly infarcted, a rate or estimated quantity of patientbrain tissue that likely will become irreversibly infarcted at a futuretime, a thrombus morphology associated with a likelihood of a thrombusdissolving at the future time, and an estimated collateral blood flow;determine an estimated transport time to transfer the patient to atreatment facility and an estimated treatment time for receivingreperfusion at the treatment facility; and dynamically determine apatient assessment profile by: processing the patient clinicalinformation, the patient brain imaging profile, the estimated transporttime, and the estimated treatment time to generate input data values;dynamically deriving weighting factors as an assessment of importance orrelevance of the input data values and assigning the weighting factorsto the input data values; deriving as output data values for the patientassessment profile using the input data values and the weightingfactors, the output data values being a probability of an experttreatment decision for transferring the patient to the treatmentfacility and providing the reperfusion at the treatment facility, and avisual representation of the thrombus morphology, the estimatedcollateral blood flow, and an estimated quantity of brain tissue thatwill likely become irreversibly infarcted after the estimated transporttime and/or the estimated treatment time using the rate or the estimatedquantity of patient brain tissue that likely will become irreversiblyinfarcted at the future time. The imaging system has an output device tooutput the patient treatment protocol as clinical decision supportinformation.

In some embodiments, the imaging system determines that the patient isalready at the treatment facility and updating the visual representationwith the estimated quantity of brain tissue that will likely becomeirreversibly infarcted after the estimated treatment time for receivingreperfusion.

In some embodiments, the imaging system determines a patient clinicaldata profile identifying an age or age range for the patient and astroke severity, the stroke severity defined on a scale of mild,moderate and severe or based on physician heuristics, and determiningthe patient assessment profile using the patient clinical data profileas input to the system model.

In some embodiments, the imaging system determines the time elapsedsince the onset of stroke symptoms as an additional input data value forthe patient assessment profile.

In some embodiments, the imaging system determines the patient'spre-morbid status, general health and co-morbidities as additional inputdata values for the patient assessment profile.

In some embodiments, the imaging system determines the patient'sadvanced directives as an additional input data value for the patientassessment profile.

In some embodiments, the imaging system determines current medicationsand/or medical history of patient that significantly influence decisionmaking as an additional input data values for the patient assessmentprofile, including blood thinners and recent surgery.

In some embodiments, the imaging system provides an imaging interface toconnect to an imaging device to receive the brain scan image files, theimaging device selected from the group consisting of a scanner, apicture archiving communication system network, and a cloud imagestorage device.

In some embodiments, the imaging system determines the estimatedtransport time and the estimated treatment time comprises determining arequired treatment for the patient and identifying one or more availabletreatment facilities based on available treatment services andequipment, available treatment times, available transportation type andthe required treatment of the patient.

In some embodiments, the imaging system continuously updates the patientassessment profile using a feedback loop based on additional input datavalues including configurations for the current physician and healthsystem, additional available patient and health system data, changingconfigurations for the physician and health care facility, updates forthe one or more weighting factors, control commands received from adisplay device displaying the visual representation.

In some embodiments, the imaging system continuously validates thepatient assessment profile and the input data values using current andfuture clinical trial datasets.

In some embodiments, the imaging system continuously validates thepatient assessment profile by receiving additional data and results onadjuvant therapies including neuro-protection and augmented thrombolytictechniques to change physician and health system heuristics.

In some embodiments, the imaging system receives threshold data for ahealth care provider to update and customizes the patient assessmentprofile, the weighting factors, and the input data values for the healthcare provider, the health care data including number of treatmentcenters providing endovascular treatment, staff availability, and othercurrent health care metrics.

In some embodiments, the imaging system continuously validates thepatient assessment profile further comprises determining a rate of braintissue death using collateral assessment on CTA, CT Perfusion, MRI, TCD,EIS, or a combination of thereof.

In some embodiments, the imaging system continuously validates thelikelihood of the thrombus dissolving the over future time is determinedby one or more techniques of measuring thrombus morphology such as asize of the thrombus, length of the thrombus, surface area of thethrombus, volume of the thrombus, and permeability to blood flow of thethrombus.

In some embodiments, the imaging system continuously validates alikelihood of the thrombus dissolving with administration of athrombolytic drug using the thrombus morphology and the collateral bloodflow, the patient treatment protocol indicating the likelihood of thethrombus dissolving with administration of the thrombolytic drug.

In some embodiments, the imaging system continuously validates theoutput data values of the patient assessment profile that indicates acomparison between risks of the administration of a thrombolytic drugand risks of endovascular treatment, the risks including a bleeding riskand other potentially major risks associated with thrombolytic drugadministration and a treatment risk of not being able to administer theendovascular treatment or not successfully providing the endovasculartreatment.

In some embodiments, the imaging system determines the collateral bloodflow is using mCTA, T₀ and T_(max) values.

In some embodiments, the imaging system determines the patient brainelectronic images using one or more imaging modalities selected from thegroup consisting of CT scan, multi-phase CTA, and CT perfusion, MRI,TCD, US, EIS and other imaging modalities.

In some embodiments, the imaging system determines the patient treatmentprotocol as selected from the group consisting of: transferring thepatient to the treatment facility for treatment with endovasculartherapy; transferring the patient to the treatment facility for directtreatment without additional or repeating brain scans; retaining thepatient at an initial treatment facility for treatment with athrombolytic drug; and retaining the patient at the initial treatmentfacility.

In some embodiments, the imaging system is configured to: receiveadditional patient, clinical and imaging data for stroke patients;update the input data values using the additional patient, clinical andimaging data for stroke patients; and update patient treatment protocolusing machine learning and the additional patient data, health systemdata, the updating by applying additional weighting factors to theupdated input data values.

In some embodiments, the imaging system determines the treatmentprotocol as the visual representation on time-based a ComputedTomography Perfusion (CTP) map interface.

In some embodiments, the imaging system determines the treatmentprotocol as one or more of an automated prediction of thrombuslysability using the thrombus morphology, an automated quantitation ofcollateral status on a CTP map and on multi-phase CTA and an automatedassessment of severe hypoattenuation on non-contrast CT.

BRIEF DESCRIPTION OF THE DRAWINGS

In the figures, embodiments are illustrated by way of example. It is tobe expressly understood that the description and figures are only forthe purpose of illustration and as an aid to understanding.

Embodiments will now be described, by way of example only, withreference to the attached figures, wherein:

FIG. 1 is a schematic diagram showing a triaging tool and interaction ofa patient and medical facilities according to some embodiments.

FIG. 2 is a flow chart diagram of a process for an automated triagingdecision support tool according to some embodiments.

FIGS. 3A and 3B are screenshots of visual representations identifyingthe presence of a permeable thrombus.

FIG. 4 provides graphs of thrombus dissolution rates based onsemi-automated detection of permeable thrombus and automated detectionof collateral flow. Automated detection may be used in thrombusdissolution or recanalization rates of the tool.

FIG. 5 is a table for an example of a multivariable logistics regressionmodel that uses constructs in FIG. 4 to determine thrombus dissolutionrates.

FIG. 6 is a screenshot of a visual representation of patientcollaterals.

FIG. 7 is a screenshot of visual representations of image slices frommulti-modal imaging including non-contrast CT, multi-phase CTA and CTPerfusion. The bottom panel shows final infarct. The tool may use any orall of these imaging modalities to estimate infarct over time.

FIG. 8 is a screenshot of visual representations of image slices forfrom automatic generation of arterial input function for use in CTPerfusion.

FIG. 9 illustrates visual representations of time-based CT Perfusionthresholds.

FIG. 10 illustrates a visual representation charts used to construct thetime based model for infarct growth using CT Perfusion according to someembodiments.

FIG. 11 is a screen shot of a visual representation of an image slice ofa CTP study according to some embodiments that demonstrates techniquesfor patient motion correction.

FIG. 12 is a screen shot of a visual representation of image slices of aCTP study that shows patient (e.g. head) motion in the Z-axis.

FIG. 13 is a screen shot of a visual representation of image slices of aCTP study showing the effect of z-axis motion on perfusion parametermaps of a CT Perfusion Study. The CBF and Tmax maps with and withoutz-axis motion correction are shown together with the mean value within acircular region of interest within the stroke affected hemisphere andcontralateral hemisphere.

FIG. 14 is a screen shot of visual representations of image slices froman application of time-based infarct growth according to someembodiments.

FIG. 15 is a screen shot of a visual representation of an example of a3D clot segmentation from non-contrast CT (Left Inset) using proposedautomated technique.

FIG. 16 is a schematic of triage computing tool or device according tosome embodiments.

FIGS. 17 to 21 are schematics of example systems with the triage toolaccording to some embodiments.

FIG. 22 is a flow chart diagram of the development process for anautomated triaging decision support tool according to some embodiments.

DETAILED DESCRIPTION

Embodiments described herein may provide methods, systems, and apparatusfor triaging decision support tools that can assist in thedecision-making at a hospital or other health care facility fortreatment of stroke patients, such as for example, whether or not toimplement endovascular therapy, transfer the patient to a facilitycapable of endovascular therapy, administer thrombolytic drugs, orperform additional imaging.

FIG. 1 is a schematic diagram of the triaging process from home tocommunity hospital to the tertiary hospital in a hub and spoke strokecare model as an illustrative example embodiment. The triaging decisionsupport tool 22 may make the process more efficient.

As shown in FIG. 1, a patient 10 in a peripheral community 12 may besuffering a stroke and transferred by paramedics 14 to an emergency room16 a of a community hospital 16. At the community hospital 16, a scanneror imaging device may generate one or more brain and neurovascular brainscan electronic images 16 b (in a variety of imaging modalities) toprovide electronic data to a computer device or decision support tool 22that seeks to automatically answer the question 16 c whether the patientshould be transferred using a transportation vehicle 18 (of varioustypes) to a tertiary hospital 20 and time to transfer 16 d. The tool 22may implement machine learning techniques based on expert physiciandata, clinical data, imaging data, and so on. Other automated answersmay also be provided as described herein. For this illustrative example,the decision support tool 22 receives brain scan electronic images 16 bas input from an imaging device, estimated time data (e.g. time totransfer to facility 16 d, time for treatment), patient clinicalinformation 24, and other input data.

The decision support tool 22 may be configured to provide an automatedtool that takes into account various imaging and clinical factorscaptured as input data sources in providing information to assist aphysician in determining the answer to the question “Should this strokepatient be sent to the hospital where endovascular therapy is availableright now?”. The decision support tool 22 (which may be referred toherein as the tool for simplicity) may be updated and refined usingheuristic and machine learning techniques. The tool 22 may implementmathematical and statistical models for aspects of embodiments describedherein. The tool 22 may also provide an expeditious and appropriateautomated answer or other decision support information for a healthcareprovider. The possible automated answers may include:

-   -   Transfer the patient as soon as possible to the tertiary        hospital for treatment with endovascular therapy. This may also        involve a treatment with thrombolytic drugs despite a low (but        non-zero) likelihood of successful recanalization of the        occluded vessel with this therapy.    -   Transfer the patient as soon as possible to the tertiary        hospital for endovascular therapy but do not treat the patient        with the thrombolytic drug given futility and increased harm        with the latter.    -   Do not transfer the patient. Keep the patient at the primary        hospital and treat him/her with thrombolytic drugs only as there        is a high likelihood of successful recanalization of the        occluded vessel with this therapy.    -   Do not transfer the patient because a large or critical volume        of the brain is already irreversibly damaged or will die before        the patient could be transferred and undergo successful        treatment at the tertiary hospital.    -   Do not transfer the patient. Keep the patient at the primary        hospital and treat him/her with thrombolytic drug only because        the patient is not eligible for endovascular treatment for        reasons of pre-morbid medical conditions, arterial anatomy or        other medical reasons.

Various example factors that are input into the tool 22 and system modelmay be divided into example categories: 1) clinical factors, 2) imagingfactors, 3) estimated time required to transfer the patient to thetertiary hospital (or other care facility), and 4) estimated time toreceive treatment.

FIG. 2 is a flow chart diagram of an illustrative process for anautomated triaging decision support tool according to some embodiments.

Input Information—Clinical Factors

At 202, the tool 22 receives clinical data for a patient. The tool 22may also receive clinical data for other patients to help construct andvalidate the statistical and mathematical model configuration as will bedescribed herein. The tool 22 may complete missing data points usingestimate and computed means for example. As additional input databecomes available the tool 22 may adjust to the additional input dataand provide updated output results.

Illustrative example clinical factors that may input into the tool 22include:

-   -   The age of the patient.    -   Severity of the patient's clinical situation.    -   Duration of the patient's symptoms.    -   The patient's pre-stroke functional status.    -   Patient's advance directives and expectations regarding quality        of life

Further information regarding a computer application that can providedirectives and patients' expectations is provided, for example, inInternational Patent Application Serial No. PCT/CA2014/050899 entitledSystems and Methods for Obtaining and Displaying Medical Data to AssistDecision Making During a Medical Emergency the entire contents of whichis hereby incorporated by reference.

The age of the patient may be determined or estimated when a patientarrives at the hospital. The patient data may be part of a hospitalinformation system (HIS) or a radiology information system (RIS) andintegrated with or accessed by the tool 22. Nursing personnel orphysicians may collect primary information on the stroke severity usinga simple standardized scale, such as mild, moderate or severe. The scalemay also be a scale of values or factors. The severity scale may takeinto account the patient's comprehension, level of consciousness, speechand motor function of face, arm and leg, for example. This may be doneusing the NIH stroke scale as another example.

The duration of the patient's symptoms is input in minutes based on theinformation available to the nursing personnel or physicians fromwitnesses and/or emergency response personnel. In some cases, a precisetime of onset of stroke symptoms is not known. In such cases, the lastseen normal time may be provided as input.

The patient's pre-stroke functional status may be determined using aquestionnaire that takes into account the patient's capabilities priorto the current event, such as the Barthel Index which records thecapacity to perform activities of daily living. In some cases, thisinformation is not available due to the emergency nature of thepatient's condition. In such cases, that information is inputted as“unknown” and the system model may adapt accordingly.

The patient's pre-stroke advanced directives may be determined by thetreatment medical team (physicians, nurses), may be available on-line aspart of a health record system or a patient database. In some cases,this information is not available due to the emergency nature of thepatient's condition. In such cases, that information is inputted as“unknown” and the system model may implement machine learning to adaptaccordingly.

There may be a variety of reasons why the initial patient clinical dataset is incomplete. For example, a patient may not conscious, no familyaround, patient is not cooperative, patient cannot be given IV contrast:e.g. contrast allergy, poor kidney function, imaging attempted but ofpoor quality due to patient motion, institutional policy (e.g. do not doCT perfusion), equipment issues (too old, some things cannot be done,equipment failed halfway through the procedure) and so on. Anotherfactor may be the condition of the patient, such as a fluctuatingpatient and improving patient.

At 204, the tool 22 receives imaging data for a patient including theelectronic images from the patient brain scan.

Input Information—Imaging Factors

Several inputs in the tool 22 may be based on the electronic images orscans produced from various brain scan or imaging devices. The imagingmay be conducted when the patient arrives at the hospital, for example.Different imaging modalities, technologies and formats may be used, asdescribed herein. Different imaging technologies may also providemeta-data about the patient in addition to electronic images.

For example, electronic images may be generated from a CT scan of thepatient's brain to rule out a hemorrhagic stroke (i.e. a bleed) prior toproceeding with additional CT scans to determine if the stroke is anischemic stroke. The image set may be updated over time. The physicianmay also use magnetic resonance (MR) brain imaging modality, or anotherbrain and neurovascular imaging device. The tool 22 may work with bothCT and MR, for example. Further examples of other imaging techniquesthat the tool 22 may work with include electrical impedance spectroscopyfor imaging brain to provide realistic non-invasive assessments of thebrain including occluded arteries. TCD is also another exampletechnique.

The tool 22 may automatically process the images to generate a patientbrain imaging profile. The imaging profile may include the images, andadditional meta-data identifying a quantity and eloquence of braintissue that is irreversibly infarcted, a rate or estimated quantity ofpatient brain tissue that likely will become irreversibly infarcted at afuture time, a thrombus morphology associated with a likelihood of athrombus dissolving at the future time, and an estimated collateralblood flow.

Further example imaging factors include:

-   -   The amount and location of brain tissue that is already        irreversibly damaged and the amount and location of brain tissue        that will likely die before the time the patient reaches the        tertiary hospital from the community hospital and could undergo        successful treatment.    -   Presence of a target thrombus causing a proximal intracranial        occlusion.    -   The likelihood of the thrombus in the patient's head dissolving        quickly and blood flow be adequately restored (reperfusion) with        the administration of the thrombolytic drug.    -   The risk of giving the thrombolytic drug compared to the risks        of endovascular treatment.    -   The likelihood of success of endovascular treatment in restoring        blood flow (reperfusion) based on access factors e.g. severe        tortuosity.        Determination of the Amount of Irreversibly Infarcted Brain        Tissue and the Amount that Will Likely Die

In some embodiments, the tool 22 uses techniques to automaticallydetermine the amount of brain tissue that is likely irreversiblyinfarcted at the time of initial brain scan. The tool 22 uses techniquesto also automatically determine the amount of brain that will likely diein the time it takes for the patient to be transferred from thecommunity hospital to the endovascular capable hospital. This automatedimage processing may use different types of brain scans and imagingmodalities to determine metrics of the imaging profile such as anon-contrast CT scan; multi-phase CTA; CT Perfusion or MRI, MRPerfusion, and MR angiography. Example metrics are described herein suchas the amount of brain tissue irreversibly infarcted at time of scan andestimated to be irreversibly infarcted after transfer to endovascularcapable hospital.

The tool 22 is capable of deriving triaging decisions from each of thesescans individually but can use other scans if and when available toincrease accuracy around the triaging decisions and provide more nuancedinformation. The tool 22 is flexible which is relevant from an acutestroke treatment perspective. Sometimes, the patient's clinicalsituation is such that a multi-phase CTA or CT perfusion is notavailable because the patient is allergic to the contrast dye used inthese scans or the patient has kidney disease. The tool 22 may use thenon-contrast CT data to make the triaging decision. Other times, thepatient moves on the scanner or is agitated, thus resulting in only onetype of scan available, the other scans being of poor quality due topatient motion. The tool 22 may identify poor quality images and use theavailable information from the best scan to make a triaging decision.Some hospitals, due to logistics or physician preferences, may only useone or two types of scans. The tool 22 is flexible enough to providerelevant triaging information using the scans the hospitals has accessto.

In some embodiments herein, the tool 22 may use non-contrast CT scanimages which is a brain scan image available in most treatmentfacilities or hospitals with CT scanners. A non-contrast CT scan imagemay be used to determine the amount of brain tissue that is alreadyirreversibly infarcted. As an example, the extent and volume of braintissue that is likely already irreversibly infarcted may be delineatedusing an intensity-based region-growing algorithm that assesses allneighboring regions of a segmented brain volume to determine if thoseregions should be included or not. The regions may be provided as partof the visual representation for display on a display device. If thecenters use MR imaging, the tool 22 may use diffusion imaging todetermine the amount of brain tissue that is irreversibly infarcted anda GRE (Gradient Recalled Echo) or SWI (susceptibility weighted imaging)sequence may be used to rule out bleeding risk.

Transfer may be futile if a large volume of brain at risk is alreadyirreversibly infarcted. In some embodiments herein, the tool 22 takesinto account the possibility that one or two of the three possible brainscans (i.e. non contrast CT, multi-phase CTA or CT Perfusion) willeither be unavailable or be of insufficient quality to be used. Forexample, a brain scan may not be used if a patient has moved during thescan or there is poor contrast on the images, the resultingdetermination would be discarded or given a lesser weighting in thefinal determination.

In some embodiments, for example, a single or preferably multi-phase CTAmay be used to automatically determine collateral status. Collateralsare backfilling pial vessels beyond a thrombus seen on brain scans.Patients with good collaterals may have a brain that may be saved byremoving the thrombus while patients with poor collaterals may not haveany brain worth saving in some circumstances. In case of multi-phase CTAdatasets, a temporal maximum intensity projection may be used togenerate a single CTA dataset, which is independent of the acquisitiontime. An advanced vessel segmentation framework may be employed toautomatically extract the vessels from this CTA dataset. After this, thetwo hemispheres may be automatically separated, e.g. by non-linearregistration of a brain atlas to the NCCT dataset. After separation ofthe hemispheres, the volume of the segmented vessels may be calculatedfor the affected and unaffected hemisphere. In doing so, a ratio betweenthe vessel volume in the affected and the vessel volume in theunaffected hemisphere may be calculated. Here, it is assumed that valuesclose to one indicate a good collateral situation while lower valuesindicate a poor collateral situation. This information, which becomesavailable in 4-8 pre-specified brain regions, by calculating this ratiofor each phase of the multi-phase CTA dataset, will determine collateralstatus and therefore the amount of brain that is already irreversiblyinfarcted. The automatically determined collateral score (ratio of thevessel volumes in the affected and unaffected hemisphere) on the mCTAdatasets will be validated by comparison to determine pial arterialfilling score using Spearman's correlation to help improve accuracy ofthe automatic determinations.

Information on collateral status in each brain region may also aid indetermining if that brain region will be irreversibly infarcted in thetime it takes to transfer the patient to the endovascular capable carefacility. Brain regions with intermediate collaterals may only surviveif the thrombus blocking blood supply to that part of the brain isremoved quickly. Arrival at the tertiary hospital may need to be lessthan a specific time threshold away (e.g. estimate 180 minutes) due totransport distance and availability of treatment modality for thetreatment to be effective. For example, a brain with intermediatecollaterals may only survive for an estimated time period and the timefor transfer and treatment should be less than that time to beeffective. Only a brain with good collaterals may be likely to surviveif the tertiary hospital is more than the specific time threshold (e.g.180 minutes) away. Automated regional assessment of collateral statususing the tool 22 may help physicians making this determination.Collateral assessment may also be determined from the source images ofCTP. In a facility or centre using MR imaging, an MR angiogram may beused to determine the site of occlusion and collateral status using asimilar technique as outlined above for CT scans.

In some embodiments, an image scan called CT Perfusion or CTP may beused. This scan calculates blood flow in the brain. The tool 22 isconfigured with automated software (e.g. as used and refined at steps208 and 210 of FIG. 2) that determines a probability of the amount ofbrain that is likely to be irreversibly infarcted even if the thrombusis removed very early and the probability of brain that is alive now butnot likely to remain alive over the time it takes to transfer ortransport the patient to the endovascular capable hospital. To do so, acerebral blood flow (CBF) map and a time-to-maximum (T_(max)) map of theimpulse residue function (IRF) may be automatically generated by tool 22using techniques described herein. T_(max) is defined as the sum of thetime (T₀) of the first non-zero value of the IRF plus one-half the areaunderneath the IRF (or mean transport time, MTT), in some illustrativeexamples.

In some embodiments, the tool 22 may use CT Perfusion studies (e.g.images) that include the intracranial internal carotid or basilararteries in the field of view. The z-axis (axial) coverage of a CTPerfusion study may be limited to 4-8 cm on many CT scanners availableto community hospitals. 3D registration to account for axial motion maynot be optimal as it could lead to loss of entire slices for calculationof hemodynamic maps. Instead, the tool 22 may use 2D rigid registrationto remove in-plane motion in CTP studies. After 2D registration, theremay be two automation tasks: to generate the arterial input function(AIF) and to remove motion in the z-axis for each slice. For the AIFtask, the tool 22 may first remove bone and air voxels from all slicesby thresholding the first image. The tool 22 may background subtract thetime-density curve (TDC) of each remaining voxel by subtracting thebaseline value before contrast arrives from all data points. TDCs withan area under the curve (AUC) larger than 95% of the maximum AUC of allTDCs are then classified into two groups by K-means classifiercorresponding to arteries and veins. As the mean TDC from the arterygroup may have a steeper rising slope than that of the vein group, thisfeature can be used to separate the artery from the vein group of voxels(FIG. 8 image 80). For each slice, the TDC from four connected voxelswith the highest AUC from the artery group will be chosen (FIG. 8 image82). The slice TDC with the highest AUC among all slices may be taken asthe AIF. For the removal of z-axis motion of each slice, aregion-of-interest (ROI) will be automatically generated around theentire brain after removal of the skull from the AIF task (FIG. 11 image1100). The TDC from this ROI may be baseline subtracted and normalizedby the average value before it is fitted by deconvolution with the AIFfrom the first task (FIG. 11 image 1102 and image 1104). The absolutedeviations of the fitted and the measured TDC at all time points will bedetermined (FIG. 11 image 1106). Images at time points where thedeviations are more than 0.3 will be removed from the calculation ofhemodynamic maps for this slice (FIG. 12 image 1206 and FIG. 13). Usingthe determined AIF, the tool 22 configured with CTP perfusion softwaremay then calculate the following functional maps: cerebral blood flow(CBF) and T_(max), cerebral blood volume (CBV), and MTT. As shown inFIG. 13, z-axis motion affects cerebral blood flow (CBF) and T_(max)values determined by the tool 22 configured with CT Perfusion software.Since infarct growth may be determined using CBF and T_(max) thresholds,it may be important to correct for z-axis motion

Once the above step is accomplished, the tool 22 may use CTP-Averagemaps (e.g. averages of all images of the same slice in a CTP study) tocreate tissue segmentation masks (e.g. grey and white matter masks) byremoving any cerebral spinal fluid or old infarcts as an example aspectof a visual representation. The tool 22 may separate gray matter (GM)and white matter (WM) based on pre-determined Hounsfield Unit thresholds(FIGS. 7 and 14). To remove any voxels caused by inherent noise, thesystem model will use a clustering method that will remove any singlevoxel that is not part of the confluent tissue of interest (FIG. 14 at1402). The tool 22 may then superimpose these segmentation masks ontoperfusion parameter maps created in step above (CBF, CBV, T_(max) andMTT maps) (FIG. 14 at 1404). The system model will then use GM and WMtime-dependent perfusion parameter thresholds that have alreadydetermined. Further examples are provided in Time-Dependent ComputedTomographic Perfusion Thresholds for Patients With Acute Ischemic Strokeby Bijoy Menon et al., the contents of which is hereby incorporated byreference. The tissue segmentation masks to predict current infarctvolumes and infarct volumes at different times after successfulreperfusion with IAT are arrived at as described herewith. The tool 22will use a “double threshold” technique by first applying a T_(max)threshold to define “total at-risk” tissue (T_(max)>6 seconds) and thensequentially applying the time dependent perfusion parameter thresholdsshown as visual representations in FIGS. 9 and 10 for example, and shownin a patient in FIG. 14. These time-dependent perfusion parameterthresholds may also be validated using CTP and correlative imaging andclinical data from different trial databases.

Validation may involve using the CT Perfusion datasets acquired atbaseline to generate perfusion parameter (PP) maps after motioncorrection as described herein. After this, the derived time-dependentthresholds derived by tool 22 may be applied to the PP maps to determinethe expected final infarction at different follow-up times. Availabletimed follow-up imaging (NCCT or MR-DWI images) will be non-rigidlyco-registered to baseline PP maps. Multiple neuro-radiologists(experts), blinded to the results of the PP maps, may delineate byconsensus follow-up infarct regions of interest (ROIs) on theco-registered MR-DWI or NCCT images while excluding any small vesseldisease abnormality or chronic/old infarct. The delineated follow-upinfarction volumes may be compared to that derived from PP maps with thetime-dependent thresholds using the Dice coefficient and the Hausdorffmetric.

This validated probabilistic map of the dead or irreversibly infarctedbrain tissue at different times following baseline brain scan may becorrelated with the time information for transporting the patient to thetertiary hospital, the time required for treating the patient with theendovascular procedure and the likelihood of the patient's thrombusdissolving within that time will be used to determine the amount oftissue that will likely die within that time. A final map is then madeshowing the likely area of irreversibly infarcted brain at the time ofthe endovascular procedure. Further details regarding refinement,construction and validation of the system model with be provided hereinin relation to FIG. 2 at 208, 210 and FIG. 22.

In some embodiments herein, the use of US imaging, TCD imaging, EISimaging or other scanning technology may be used to identify thelocation of arterial occlusion and the likelihood of thrombusdissolution. This location will be used to determine the target forpossible endovascular therapy.

In some embodiments herein, the physician at the community hospital mayuse visual information from the automated perfusion parameter maps orother scanning images as decision support in determining whether totransfer the patient to another treatment facility. That is, acceptablethresholds for tissue death overtime using all types of available brainscans are determined using statistical formulae based on pre-existingdatasets and derived using assessments by expert physicians. Forexample, acceptable thresholds are determined for tissue that willlikely die within 60 minutes, 120 minutes, 180 minutes, 240 minutes, andso forth.

In other example embodiments, for example in the context of fullyautomated systems, various thresholds for tissue death are used for eachavailable brain scan, along with clinical information, information ongeographic distance between community hospital and tertiary hospital,transport times and other inputs, to automatically determine whether thepatient would have been transferred if an expert physician were makingthe decision. Details of this process are described further herein.

In other example embodiments, for example in the context of fullyautomated systems, various thresholds for tissue death are used for eachavailable brain scan, along with clinical information, information ongeographic distance between community hospital and tertiary hospital,transport times and other inputs, to automatically determine if thepatient can directly be taken to the tertiary hospital's endovascularoperating suite without doing repeat imaging at that center, thus savingcosts of repeat imaging. Details of this process are described furtherherein.

In other embodiments, in centres using MR imaging an MR angiography orMR perfusion scan could be used to produce similar results. Similarly,combinations of different imaging modalities (CT, MR, TCD, US and EIS orother imaging type), depending upon availability could be used toproduce output decision support results.

The Likelihood that the Thrombus Will Dissolve Early with theThrombolytic Drug

Different example techniques may be integrated into the tool 22 todetermine the likelihood of the thrombus dissolving early with thethrombolytic drug. These techniques use information on the size of thethrombus which may be defined by thrombus length, and using permeabilityand collateral blood flow.

Thrombus Length

The length of the thrombus in the patient's brain artery may bedetermined by tool 22 using multi-modal CT imaging. The non-contrast CTmay be used to simply measure the hyperdense tubular middle cerebralartery on think axial (or other angle such as coronal or sagital) imagesthrough the circle of Willis. The tool 22 may use CT (NCCT), multiphaseCTA and/or CTP, for example. The tool 22 may use one or all of themultimodal CT modality depending upon availability and image quality. Insome example embodiments, the length of the thrombus in the patient'sbrain may be determined by tool 22 using a non-contrast CT scan. Inother example embodiments, the tool 22 may use non-contrast CT (NCCT)and multi-phase CTA and/or CTP, varying by availability and scanquality, for this purpose. The tool 22 can use the CT perfusion andmulti-phase CTA to improve accuracy of clot length determination onnon-contrast CT. Note, the tool 22 may use CT Perfusion to determineclot permeability, or other imaging modalities in other exampleembodiments.

In case of multi-phase CTA, a temporal maximum intensity projection maybe used to generate a single CTA dataset. After co-registration withNCCT, the bone tissue may be segmented in the NCCT dataset usingHounsfield value thresholds for bone tissue, for example. An advancedvessel segmentation framework may be employed to automatically extractthe vessels from this CTA dataset. Using the 3D centerlinerepresentation of this vessel segmentation, all vessel endpoints thatrepresent candidates for the proximal and distal ends of the thrombuswill be identified. The 3D course of the vessel potentially occluded bya thrombus may be approximated for each vessel endpoint using theneighboring centerline voxels directly connected to the vessel endpoint.This allows expanding the centerline locally in the direction of thepotential thrombus. This expanded centerline section may be used for aregional analysis of the Hounsfield values in the CTA and NCCT datasetalong the expanded vessel, wherein it is assumed that a thrombus isrepresented in the resulting intensity profile by an increase of theHounsfield values in the NCCT dataset and decrease of the Hounsfieldvalues in the CTA dataset.

The tool 22 may also use patient specific Hounsfield values determinedfrom the patient's non-contrast CT scan and an automatic 3D volumegrowing technique within the extracted vessel endpoint as a seed, forexample. This automatic segmentation of the thrombus will enabledetermination of the subsequent analysis of its length and morphology,surface area, and so on.

The automatic segmentation of the thrombus enables the subsequentanalysis of its morphology. Within this context, thrombus length andthrombus surface area may be determined using the above technique willdetermine likelihood of early thrombolysis. The thrombus lysis isdependent on the length and/or surface area and volume of the thrombus.Therefore, the tool 22 may calculate thrombus length, surface area andvolume of the thrombus directly exposed to the blood and thrombolyticdrug using the imaging data.

This automated method of determining thrombus morphology may bevalidated against CT data from a large patient dataset. The automaticthrombus segmentations developed by tool 22 may be compared withmanually delineated thrombus segmentations from expert independentobservers using similarity metrics like the Dice coefficient and theHausdorff distance. This validation technique may be used to improve onthe thrombus segmentation technique and the automated thrombussegmentation technique. Similar techniques may be used to determinethrombus size and morphology using MRI or TCD or other imagingmodalities based on availability.

Thrombus Permeability

A thrombus that is permeable to blood (i.e. porous) may be more likelyto dissolve quickly with thrombolytic drugs compared to a non-permeablethrombus. The system uses novel techniques to automatically determinethe permeability of a thrombus.

Automatic Determination of Thrombus Permeability Using Contrast Density

The first technique for determining thrombus permeability involvesmeasuring the change in contrast density within a thrombus using mCTAscans or source images of a CTP. Example mCTA techniques are describedin International Application No. PCT/CA2013/000761 entitled SYSTEMS ANDMETHODS FOR DIAGNOSING STROKES, the entire contents of which is herebyincorporated by reference. The location of the thrombus may bedetermined on multi-phase CTA (as an illustrative example) or otherimaging modality depending on availability. Next, contrast densitymeasurements may be taken from the thrombus segment in the time variedmCTA and/or CTP images, and a time density curve is obtained from theregion of the thrombus. The more the thrombus region increases indensity over time, the more permeable the thrombus is since the contrastis permeating through the thrombus. The rate of increase in thrombusdensity over the temporal duration of a multi-phase CTA or a CTperfusion is used to automatically determine the degree of thrombuspermeability. For example, the degree of thrombus permeability can bepresented on a four level scale: no permeability, mild permeability,moderate permeability and extensive permeability, which are thenintegrated into the algorithm of the tool 22. This is an illustrativeexample.

Automatic Determination of Thrombus Permeability Using the OccultAntegrade Flow Technique on CT Perfusion

The technique for automatically determining thrombus permeability usesCT Perfusion T0 maps to determine the forward flow through a thrombus.CT Perfusion T0 maps measure arrival time of contrast from that in areference artery (an example is the arterial input function (AIF)) as anarterial reference point in a CT Perfusion processed map. The CTPdataset is automatically realigned with CT angiographic images by tool22, as described herein, to correct for movement between the scans.

The 3D centerline representation described in herein may be used todefine the end points of the thrombus. In a following step, the averagemap by averaging all the dynamic images of a CTP study will beregistered to the corresponding CTA dataset using a rigid 3Dtransformation. As the average map and perfusion parameter maps areinherently registered with respect to each other, the same rigidtransformation will be applied to the T0 perfusion parameter map so thatthe corresponding T0 values for the proximal and distal ends of thethrombus can be determined. The distal end of the thrombus is identifiedby a higher T0 value than the proximal end. Starting from the distal endpoint, the vessel centerline is traced within a volume of interest inthe average map with the distal endpoint as the center and thecorresponding T0 values are extracted. The T0 values and correspondingdistances to the distal thrombus end point are then used to calculatethe slope of this profile using a regression analysis. The automaticmethod of determining thrombus permeability may be compared to asemi-automatic method using Bland-Altman plots for validation.

If the difference in T0 values between the proximal and distal end ofthe thrombus is small (e.g. <2 seconds) and the slope of serial T0values distal to the thrombus is significantly positive. This generallymeans there is forward flow through the thrombus, meaning the thrombushas some degree of permeability. The difference in T0 values betweenproximal and distal end of the thrombus and the value of the slope ofthe line of best fit of T0 values in the artery distal to the thrombusmay be used to indicate the degree of forward flow through the thrombus,and thus the degree of thrombus permeability, which can again bepresented on a scale.

In FIG. 3, each of images 30 and 32 illustrate a CTP T0 map. In image30, the location of the thrombus and the distal end of the thrombus isdetermined on CT angiography. In image 32, points are marked at theproximal and distal end of the thrombus as well as along the arterydistal to the thrombus. In image 34, the above CT-angiography image isoverlayed over a CTP T0 map and T0 values calculated, where a visualindication of the overlay may be provided as part of decision support.The graph 36 to the right shows example calculations that help determinethrombus porosity. A positive slope and a small difference between T0values proximal and distal to the thrombus indicate a porous thrombus(FIG. 3 at image 30). A negative slope and a large difference between T0values proximal and distal to the thrombus indicate a non-porousthrombus (FIG. 3 at image 32).

Collateral Blood Flow

The tool 22 may also use T_(Max) (e.g. T0+½ of Mean Transport time) mapfrom a CTP scan to quantitate collateral flow more precisely. A smallerT₀ value indicates that flow to the ischemic region is taking a moredirect route while a smaller MTT indicates that once arrives at theischemic site, blood is flowing relatively quickly through the region.This method of quantitating collateral flow using T₀ or T_(Max) maps mayuse similar measurements of thrombus permeability. A negative distalartery profile slope as described herein may indicate retrograde flowthrough collaterals. The degree of the slope and the difference betweenproximal and distal thrombus interface T₀ values provide a quantitativeassessment of collateral status. A smaller T_(Max) value in the distalthrombus interface may indicate better collateral flow, for example.Good collaterals may be associated with higher likelihood of thethrombus dissolving early with the thrombolytic drug; poor collateralsreduce the likelihood of early dissolution of the thrombus with thethrombolytic drug significantly. The tool 22 may use automatedcollateral assessment from either multi-phase CTA or the T₀ maps alongwith thrombus length and thrombus surface area to determine probabilityof dissolving early with the thrombolytic drug. The tool 22 may alsotrack and determine T_(max) which may be defined as the sum of T₀ andone half of mean transport time (both generated by the software) as anadditional parameter to characterize collateral flow. A smaller T_(max)value may indicate better collateral flow. Accordingly, embodimentsdescribed herein may calculate the collateral flow using one or moreT_(max) values.

The probability of early dissolution of thrombus using the thrombolyticdrug may be modeled by the tool 22 as a function of thrombus morphologyand collateral status parameters (described herein) using logisticregression analysis, random forest classification, regression model anda trial patient dataset. Using logistic regression and a likelihoodratio based approach, the tool 22 may model the probability of achievingearly recanalization as a linear function of the imaging parametersidentified above. The random forest classification and regression modelis a non-parametric high-level machine learning technique useful forvariable selection and prediction. The predictive performance of thismodel will be assessed using the out of bag (OOB) error. Random forestregression and classification may provide a predictive tool that makesless stringent assumptions about data distributions, sample size, andpredictor correlations than logistic regression analysis.

The prediction models derived from logistic regression analysis andrandom forest classification and regression models may be validatedusing an internal validation approach and the same trial patientdataset.

For internal model validation, cross-validation may be used by the tool22 to adjust for optimism bias (the difference between the predictionerror for the entire cohort and the training cohort). The tool 22 mayimplement one or more training stages for machine learning. The tool 22may also conduct external validation using combined data from otherrecent patient datasets. Using the models derived and internallyvalidated in our study data, the tool 22 may obtain the predictiveaccuracy of models using the external validation data. A model with highprediction accuracy may be used as input into the tool 22.

Additional Imaging Factor: The Risks Involved with the Thrombus BustingDrug Vs. Endovascular Treatment

The third imaging factor quantifies the risks involved withadministering the thrombolytic drug to the patient compared with therisks of the endovascular procedure.

Risks Involved with Administering the Clot Busting Drug

A serious risk involved with administering the thrombolytic drug isbleeding in the brain. A likelihood of a patient bleeding in the brainafter receiving the thrombolytic drug may be determined or estimatedwith a high degree of specificity using CTP images based on the conceptof very low blood volume but high vessel permeability. The tool 22determines the probabilities of bleeding with minimal human involvementusing the techniques described herein and other imaging techniques.

For example, the tool 22 may use the non-contrast CT scan images todetermine a degree of hypo-attenuation (reduced signal) in the ischemicbrain. The affected region for automated analysis may be determinedusing techniques described herein. There is risk of bleeding into thebrain if the patient has a sub-acute stroke i.e. present after >24 hrs(e.g. a long time) from stroke symptom onset with severe ischemia incertain regions of the brain. Determination of sub-acute stroke can bemade using imaging. It is to be noted that significant hypo-attenuationon a non-contrast CT scan is often used by expert stroke physicians towithhold the thrombolytic drug from stroke patients. Hypo-attenuation inischemic brain that is similar to or lower than normal white matterhypo-attenuation may indicate severe or sub-acute ischemia in thatregion of brain; this is considered a relative contra-indication for useof the thrombolytic drug because of the increased risk of thrombolyticdrug-associated hemorrhage. The tool 22 may use the same techniquesdescribed herein to automatically determine if such a degree ofhypo-attenuation exists in the ischemic region in the brain.

There may be risks for hemorrhage for different reasons. Managementdecisions may be based on whether blood is sub-arachnoid or parenchymal,if sub-arachnoid, what is the source of the bleed, if an aneurysm, thebest way to treat it, if an AVM, what is the best way to treat this, ifparenchymal, and so on. Treatment factors may include for example, age(young, old), location (superficial, deep), underlying lesion (avm,tumour) or no underlying lesion (hypertension and amyloid angiography),active bleeding or not, availability of neurosurgical treatment optionsand medical options.

A large brain region with very poor collaterals is associated with ahigher risk of thrombolytic drug-associated hemorrhage. The tool 22 mayalso use information derived from automatic assessment of collateralstatus in different regions of the ischemic brain described herein todetermine risk of bleeding into the brain. The tool 22 may also use CTperfusion to analyze various perfusion parameters including:permeability surface-area produce (PS), very low cerebral blood volume(vICBV), very low cerebral blood flow (vICBF), mean transport time(MTT), and T_(max). These CT perfusion parameters, when available, mayalso be predictive of the risk of the bleeding into the brain with thethrombolytic drug.

Risks Involved with the Endovascular Procedure/Factors that Reduce theLikelihood of a Successful Endovascular Procedure while Prolonging theTime Taken for a Successful Procedure.

Several factors can increase the risk of the endovascular procedure ormake the administration of the procedure more difficult. These factorsinclude severe tortuosity of neck blood vessels, the presence ofsignificant carotid atherosclerotic disease that might prevent passageof an endovascular catheter, and the presence of extra- or intracranialdissection. The tool 22 may use CTA head and neck imaging to quantitateeach of the above parameters. Each of these variables prolong the timetaken to achieve a successful endovascular procedure or may completelypreclude a successful endovascular procedure. Output from thisquantitation may be used by the tool 22 to generate output results fordecision support.

Various alternative technologies may be used to receive imaging data forthe patient. For example, there may be a CT scanner in the ambulance orother emergency transport vehicle. There may be the capability to befully integrated in the ambulance based system, for example. The inputfactors may remain the same as described herein. However for outputbased on the distance to the primary care centre to the tertiary carecentre (and the corresponding estimated transmit time at step 206), theDI DO (door in door out) time at the primary care centre and previouslydescribed factors such as likelihood of clot dissolving with IV tPA, maybe used by the tool 22 for generating output for decision support toassist with decisions regarding bypassing the primary care centre ornot.

As another example, the imaging data may be received from crosssectional imaging technology in the angiography suite. This can be donein different ways. For example, there may be hybrid rooms where there iseither a CT scanner or an MR scan built in beside the angiography suite.As further example, there may be cross sectional imaging in theangiography suite itself. A patient may go straight from emergency roomto the angiography suite, and have the imaging performed to generate thebrain scan images. The tool 22 outputs the decision to a display devicein the angiography suite (or via a remote connection) and depending onthe decision made, the care providers start the procedure. Here in thetool 22 may implement the process described herein with a fewvariations. In case an option (which may be common) is being used thenone cannot obtain typical perfusion maps. Perfusion maps may give theiroutput differently (called PBP). These could be used as a surrogate forirreversibly infarcted tissue, for example. Also it is likely that thetime between imaging and reperfusion may be dramatically reduced in thisscenario which would be built into the tool 22 configuration.

For patients getting transferred, the imaging at the primary care centremay provide guidance regarding whether a detailed repeat imaging isrequired at the CSC or not. It may be based on the following factors:amount of irreversibly infarcted brain on original scan, quality ofcollaterals, and time elapsed in between the imaging and the treatmentto factor the concept of ‘shelf life of imaging’. Rather than using afixed value, this may be flexible based on factors noted herein. If theoverall time is short and the collaterals are good, the tool 22 mayprovide decision support regarding bypassing the CT scanner and MRIscanner and going straight to the angiography suite and possiblyperforming a basic head CT scan to rule out hemorrhage or other bleedingrisks. This is an example onl and other imaging technologies includeTCD, US, electrical impedance plethymosgraphy, spectroscopy, and so on,may be used.

At step 206, the tool 22 determines an estimated transport time totransfer the patient to a treatment facility. The tool 22 may alsodetermines an estimate treatment time until the patient can receive thereperfusion or other treatment at the treatment facility after transfer.

Input Factors—Time

Another general input factor in determining whether a patient should betransferred is the time factor that may be based on multiple variablesthat correspond to time estimates. The time factor takes into accountthe time required to pragmatically transfer the patient to the tertiaryhospital from the primary hospital, as well as the time required to openthe vessel in the patient's brain through the endovascular thrombectomyprocedure once the patient arrives at the tertiary hospital. Variousfactors may be taken into account in determining the time, including thedistance between the hospitals, the time of day, weather, traffic,availability of transfer vehicles and trained personnel, availability ofphysicians who can perform the endovascular procedure at the tertiaryhospital, the medical status (stability) of the patient, and more. Thesefactors may have a baseline or default value set for a particular sitee.g. if the average travel time to the tertiary health facility isapproximately 90 minutes (including patient transfer to ambulance) thenthis would be a fixed variable for that particular site. Howeveradditional factors e.g. traffic issues or weather would allow the siteto change this.

Automation

The tool 22 automates the collection of information regarding thepreviously described factors and, at 208, determines a patientassessment profile using the system model. The patient assessmentprofile may be generated by tool 22 using the patient brain imagingprofile, the estimated transport time, and the estimated treatment time.The patient assessment profile defines a patient treatment protocolindicating a probability of an expert treatment decision fortransferring the patient to the treatment facility and providing thereperfusion at the treatment facility. The patient assessment profiledefines a visual representation for display on a display device, wherethe visual representation may visually indicate the thrombus morphologyand an estimated quantity of brain tissue that will likely becomeirreversibly infarcted after the estimated transport time and/or theestimated treatment time using the rate or the estimated quantity ofpatient brain tissue that likely will become irreversibly infarcted atthe future time.

At 210, the tool 22 may be refined with additional data about thepatient and other clinical and imaging data using machine learning,feedback, and validation data, as will be described herein. For example,FIG. 22 at 2218 references validations and feedback from multipleclinical data and imaging data sets as well as expert physician decisiondata.

At 212, the tool 22 outputs decision support information to help theend-user (i.e. the physician in the primary hospital) make anexpeditious and appropriate decision on the triage of his/her patient,i.e. to decide whether the patient should be triaged from the primaryhospital to the tertiary hospital for the endovascular procedure. Theoutput may include the visual representation of the patient assessmentprofile on a display screen as described herein. The information inputinto the system may be collected using as little input from thephysician as possible given an emergency situation and time limitations.Physician/health care personnel involvement may generally be limited toproviding clinical information such as the patient's age, strokeseverity, stroke onset time and side of stroke involvement.

Decision Support Tool

FIG. 22 is a flow chart diagram of the development process 2200 for atool for automated triaging decision support according to someembodiments.

At 2202, the tool 22 (or separate and connect system component) receivesimaging data from one or more imaging modalities such as CT, MRI,multi-phase CTA, perfusion, and so on. Other clinical data may also beprovided to tool 22. Examples of image data is described herein.

At 2204, the tool 22 may process the imaging data to generate anintermediate data set regarding a thrombus, collaterals, infarcts, andinfarct growth in the brain scan images. Examples of image processing isdescribed herein.

At 2206, the tool 22 automatically constructs or refines the data setand generates decision support information as described herein. The tool22 automates the collection of information at 2204 regarding thepreviously described factors to determine a patient assessment profile.The patient assessment profile may be generated by tool 22 using thepatient brain imaging profile, the estimated transport time, and theestimated treatment time. The patient assessment profile defines apatient treatment protocol indicating a probability of an experttreatment decision for transferring the patient to the treatmentfacility and providing the reperfusion at the treatment facility.

At 2208, the tool 22 determines additional patient metrics such asthrombus morphology, permeability, vascular segmentation, collateralassessment, baseline infarct size, severity and growth over time, andrisks for treatment. This data is provided at 2210 to further constructor refine the system model.

The tool 22 receives available patient data including additionalclinical and imaging data (at 2212), data regarding transportation time(at 2214), and data regarding health care facilities including availabletreatment services and treatment times (at 2216). The data is alsoprovided as input to refine data sets used by the tool 22 to generateoutput results for decision support.

At 2218, the tool 22 further derives and validates the system modelusing additional clinical datasets and expert physician heuristics.

At 2220, the tool 22 generates and provides output data includingtriaging decision support, a flag that additional imaging is required,and risk analysis. This information is also used by the tool along withphysician feedback to further refine the system model continuously. Forexample, different weight factors may be linked to different inputfactors to provide an indication or assessment of their importance. Asan example, if a large portion of the brain is irreversibly infarctedthen transfer and treatment may be futile regardless of the values forother input factors. As another example, if the patient has goodcollaterals this may be linked with a high weighting to indicate theimportance of this data value when deriving decision support astreatment may be more likely to provide a good outcome. In contrast, apatient with poor collaterals may be a very relevant input factor assuccessful treatment may be less likely. Accordingly, different inputfactors may be assigned different weighting factors based on theirimpact or relevance to the decision support output results. As noted,feedback from expert physicians may be used to refine the weightings andvalidate the output results. Further, additional imaging and clinicaldata sets may be used to refine the tool 22. Various other examples aredescribed herein. The weighting and refinement enables the tool 22 toadapt to different data sets, feedback and results as received as partof machine learning. This creates a feedback loop for refinement of thetool 22.

Other types input information detailed herein may be provided as inputdata into the system model to determine the probability that a patientwill be triaged by an expert stroke physician. Each of the input factorsdescribed, specifically the clinical, imaging and time factors are inputinto the system. The system model may be built in the followingillustrative example manner.

For heuristics, expert stroke physicians may independently examineclinical data and output from the automated imaging techniques describedabove i.e. probability of early dissolution of thrombus with thethrombolytic drug, estimated baseline infarct volume and infarct growthover pre-specified time periods (60 mins, 90 mins, 180 mins and >180mins) in a randomly selected sample of many 250 patients from multiple atrial patient dataset. The expert will examine each dataset in a randomorder. Unique to the model building exercise, the experts will also beprovided with incomplete information (e.g. A missing CT perfusion scanor a missing non-contrast CT scan or unknown time of stroke onset) todetermine how a triaging decision is made in the absence of some pieceof information. Each expert will then decide whether a patient shouldhave been triaged or not using the available information. The tool mayuse predictive machine techniques to assess a probability of agreementamong the expert decisions at each step using an unweighted Fleiss Kappastatistic, for example. This may estimate a measure of the extent towhich agreement among the experts exceed what would have been expectedif they all made their ratings completely randomly. Consensus decisionsmay be input into the model.

As another step in building the tool 22, the probability estimates ofearly dissolution of the thrombus with the thrombolytic drug, baselineinfarct volume and estimated infarct volume at the time the patientreaches the tertiary hospital from the community hospital andpatient-specific information like age, stroke severity, and baselinefunctional status whether the patient has contra-indications foralteplase or other thrombolytic drugs (e.g. Is on a blood thinner or hasa bleeding disorder) will form input variables of a random forestclassifier and regression model. The dependent variable for these modelswill be the triaging decisions made by experts. Wherever expertsdisagree, the tool may use an adjudicated consensus triaging decisionwill be used. The accuracy of the predictive model for triaging will beassessed using the out of bag prediction error from the random forestregression. The tool 22 output results may be validated using a 10-foldcross-validation methods to determine the accuracy of these models inpredicting the triaging decision made by experts. Using the modelsderived and internally validated from the trial patient dataset, thetool 22 may also obtain the predictive accuracy of this risk predictionmodel using an external validation dataset. This predictive accuracy sodetermined will be available to all users in an earlier version of thetool 22 or system model.

The tool 22 may use transportation time data available through regionalhealth services and geographic information systems (GIS) to determinethe time to transfer the patient. The final model will also use anyavailable regional health data like median door-in-door-out time incommunity hospitals and median door to groin puncture and reperfusiontimes in multiple tertiary hospitals within a 500 km radius of thecommunity hospital and staffing patterns in surrounding tertiaryhospitals (i.e. availability of specialists 24 hours 7 days a week), toprovide the physician at the community hospital guidance on whichhospital to refer the patient to increase chances of good outcome.

The tool 22 may also have the capability to modify the output based onmissing or non-contributory information. For example, if the patient hasa regular non-contrast CT head scan, a multi-phase CTA scan, and a CTPerfusion scan, but the CTP scan is degraded by patient motion andtherefore unusable, the tool 22 will recognize that the CTP scan isnon-contributory and modify the output of the model accordingly. Inanother example, if stroke onset time is missing, or a hospital is notable to perform a CTP or mCTA scan, the model will account for thiswhile providing an output constrained by that condition. In addition,the tool 22 will be able to incorporate multiple imaging technologytypes in addition to CT scans, such as MR images, trans-cranial Dopplerultrasound, electrical impedance spectroscopy or other brain andneurovascular imaging technology that is or becomes available. The tool22 will recognize the available information and keep or reject imaginginformation depending upon quality and type, and modify the output ofthe model accordingly. The tool 22 may give a confidence interval (orerror rate) on the output. Based on testing of the model it is possiblethat missing critical information may dramatically increase the errorrate. Alternatively it is also possible that in many situations e.g.absence of CT perfusion, information may not dramatically affect theoutput.

The tool 22 may continue to refine the model at step 210 (shown asfeedback loop 2210, 2218 and 2220 of FIG. 22) using machine learning andimprove its predictive accuracy using new information that will beavailable when the product is being tested real time and when theproduct is in clinical use. This continuous feedback process will happenso that tool 22 will allow community hospitals and physicians to providefeedback information on appropriateness of triaging decisions made usingthe tool 22. The community hospitals will in many cases, use feedbackthey receive from tertiary hospitals that they referred patients to. Inaddition, the model will be validated every two years with new trialdatasets that are available nationally and internationally. The patientassessment profile may be updated at 208 using the refined system model.Further, future determinations of patient assessment profiles will usedthe continually refined system model which may improve accuracy overtime and use. This may be shown in FIG. 22 as a feedback loop from 2218and 2220 to 2210.

As described, the tool 22 may refine as additional data is available.The tool 22 may provide an incremental prediction of outcome as databecome available. For example, as new data is available, such asclinical, historical, observed, or from imaging devices, the new datawill arrive into the tool 22 in a necessarily sequential series overtime (e.g. over 30 minutes). The output then is continually updated asnew data become available. The tool 22 can then trigger a thresholdrecommendation to treat or to transfer (or both) the patient beforefurther data are gathered. Other example feedback may be provided tocontinuously refine and update the output results of tool 22. Thetreating team will have the ability to change settings on the outputbased on their overall treatment strategy, distance and relationshipwith the care facility. This is especially relevant e.g. if theparamedic team stays with the patient while the decision is being made.In that case, the sooner the decision is made the less is the wastage oftime of an extremely valuable resource (the paramedic team). So the teamat the primary care facility, could decide if the output is above say80% (as an illustrative example) for transfer, the technician may stopall further work-up and focus our energies on the transfer. This maybecome relevant in the extreme situations. For example, a 40 year oldcomes in with a massive stroke onset 1 hour ago. In this case the onlyinformation that one needs to cross the threshold of 80% is a plain CThead to rule out a hemorrhage. This may be implemented using theweighting factors. This information goes over to the tool 22 andimmediately the software shows the output as green or good as it crossedthe pre-determined threshold set up by the treating team. All furtherimaging work up is immediately stopped based on the output. As anotherexample, consider a 65 year old otherwise healthy person comes in with asevere stroke (NIHSS 18) who has known atrial fibrillation and is onCoumadin. INR performed 4 days ago was 2.7. This patient has notreatment options at the primary care facility. As such very littleinformation would be needed to make transfer besides a scan to rule outhemorrhage. These are illustrative examples of the feedback andweighting process.

The tool 22 may modify itself to various geographical locations,countries and health systems using machine learning from informationthat is available from each of these systems. Thus the system model willadapt itself to the health system, province, country or geographicaldisposition in which it is located. This model improvement exercise willfollow the same principles outlined herein. Error rates are also builtinto the tool 22 to give an overall degree of confidence to decisionmaking.

The tool 22 may also adapt using machine learning algorithms techniquesthat may adapt to changing imaging technology and the accuracy andvalidation of various imaging parameters; changing transportationinfrastructure; organization and speed of treatment at the tertiarycentre; improvement in endovascular treatment resulting in faster andmore robust reperfusion; and the development of adjuvant therapies (suchas neuroprotection e.g. hypothermia and various pharmaceutical agents)that can be administered during transit or transport that can slow downthe rate of brain death.

Referring back to FIG. 2, at 212, the tool 22 may output the patienttreatment protocol as clinical decision support information for displayon a display device, for storing on a storage device, or fortransmission to another processor using a transmitter. These are exampleoutputs showing illustrative tangible results that may be provided bytool 22. For example, a visual representation may be provided on thedisplay. This may align with step 2220 of FIG. 22. The output data maybe updated using feedback, additional data, machine learning and otherrefinement processes implemented by tool 22.

Output

The output of the tool 22 can be tailored to the specific needs of theend-user. For example, some end-users may only want a yes/no decision onwhether to transfer the patient. In this case, the tool 22 may provide ayes/no decision along with confidence intervals on the precision aroundthe decision. The type, amount and format of output may be configurableby a specific user or health care facility. On the other hand, forend-users who prefer to have more information, the tool 22 may alsoprovide the following illustrative example information:

-   -   a) the amount of irreversibly infarcted brain tissue;    -   b) the amount of tissue that is likely to die by the time the        patient reaches the tertiary hospital and undergoes the        endovascular procedure;    -   c) the eloquence of the tissue (weighting by functional        importance of the brain tissue at risk) that is likely to die by        the time the patient reaches the tertiary hospital and undergoes        the endovascular procedure;    -   c) where the thrombus is and how large (eg. volume) the thrombus        is;    -   d) the probability that the thrombus will dissolve early with        the thrombolytic drug;    -   d) the risks of bleeding into the brain with the thrombolytic        drug; and    -   e) the probability of success with the new endovascular        procedure.    -   f) The need to repeat a brain scan at the tertiary center.

Case Scenario

The following case scenario is provided as an illustrative example. An80-year-old male was at a grocery store at 9 pm when he fell down.Onlookers tried helping and found he was not able to speak or move theright side of his body. They called the paramedics who reached the storewithin 10 minutes. The paramedics diagnosed stroke and immediately tookthe patient to the nearest community hospital that was 20 miles away. Adoctor in the Emergency Room saw the patient within 45 minutes of strokesymptom onset. The patient had a CT scan with CTA and CTP of the brainwithin the next 5 minutes.

The doctor now has to make a clinical decision. He needs to decide ifthe patient should be treated at his hospital with an intravenousthrombolytic drug or whether he transfers the patient to the nearesttertiary care hospital. This tertiary care hospital has facilities toremove the thrombus using the new endovascular procedure; the hospitalhowever is 50 miles away and will take around 90 minutes to reach.Besides, he will have to spend another 15-20 minutes trying to contactthe specialist there before he can make a decision to transfer thepatient to that hospital. The doctor also does not entirely understandthe risks of treating the patient with either the thrombolytic druglocally or with the new procedure at the tertiary care hospital. He onlysees such stroke cases infrequently he does not have a radiologistspecialized in reading such scans at his hospital at 10 pm that night.The family accompanying the patient also wants to understand the risksand benefits with all options.

In a normal scenario, the following outcomes may be likely:

-   -   A) The doctor tries to contact the specialist at the tertiary        hospital. He is able to contact the specialist in 10 minutes.        The specialist wants to know clinical details on the patient and        wants to look at the brain scans. The doctor uses a        sophisticated tele-radiology solution to have the specialist at        the tertiary care center look at the scans. The specialist takes        another 20 minutes to access this system and convey a treatment        decision to the doctor. It is already 30 minutes after the        initial CT scan. Treatment and transfer are delayed by 30 to 40        minutes.    -   B) The doctor is taking a lot of time trying to contact the        specialist. The family is increasingly frustrated and wants to        know why there is delay. The doctor decides to administer the        thrombolytic drug and transfer the patient to the tertiary care        hospital. After the drug is administered and the patient is        being transferred, he hears from the specialist. The specialist        tells him the scans suggest that sending the patient to the        tertiary care hospital will be futile and the risk of bleeding        in the brain may be high.    -   C) The doctor decides to give the thrombolytic drug 30 minutes        after the baseline scans after talking to the specialist. The        specialist tells him to transfer the patient to the tertiary        care hospital. After reaching the tertiary care hospital, the        specialist discovers that the thrombolytic drug has dissolved        the thrombus and the patient does not need the endovascular        procedure. The specialist now transfers the patient back to the        community hospital. Lots of resources are spent and the family        is frustrated that the physicians did something futile by taking        the risk of transferring the patient when the weather was bad.

In the above scenarios, the tool 22 can help in this and many othersituations by guiding the community physician in making the correctdecision quickly. The tool 22 may tell the community physician if thepatient has had a stroke, how much brain it has involved, whether thepatient would benefit from getting the thrombolytic drug, if the patientwould benefit from being transferred to a tertiary hospital and what isthe likelihood of the patient benefiting from either the thrombolyticdrug or such a transfer. The community physician can be increasinglyconfident of his decisions; he can call the tertiary care hospital afterhe has made appropriate decisions, thus not wasting time initiatingvital treatment decisions. He can explain to the accompanying family therisks and benefits of his decisions. The community physician is nowcapable of making decisions that would only otherwise be made at ahighly specialized center. The tool 22 has helped bridge the knowledgegap and has helped the patient by getting him access to the righttreatment expeditiously (significantly quicker and at a fraction of thecost of expensive tele-radiology solutions).

The output can be provided on a display device and in a format of choiceby the team and/or the individual based on health facilityconfigurations. Expected commonly used formats, singly or two or moreconcurrently, could be

-   -   Email attachment (to the individual or the whole treating team)    -   Texting Text messaging    -   Web-based system of display (e.g. Alternative apps or        applications such as Whatsapp™ or other messaging apps or        specialized products for this purpose)    -   Dedicated hospital based computers through a virtual private        network (VPN)    -   Simultaneous consulting mechanism to a physician at the        comprehensive stroke center by providing them with the data

The output would have the requisite level of anonymization to meet HIPAAguidelines for anonymity to meet relevant privacy legislation, such asthe United States, Health Insurance Portability and Accountability Act(HIPAA).

Additional strategies would be in place to prevent error of patientrecognition by the team.

-   -   This could mean direct communication: the two different parts of        the team have a phone conversation to ensure correctness of        patient data    -   An additional anonymization software that creates a new ID which        is sent separately from the images.    -   Strategies such as password protection.

The output may or may not contain images but may provide visualrepresentations as decision making support.

The output may have the ability to modify factors on the fly e.g. thepatient is 72 years old but is extremely healthy and recently ran amarathon using weighting factors that may dynamically adjust based onfeedback on provide output results. In the judgment of the medical team,the biological age of the patient is 50 years (much less than thechronological age of 72), the treating team can see the influence ofthis age change using an adjustment to the weighting factor linked tothe input factor for age and the output result will in turn dynamicallyupdate on the fly based on the weighting factor adjustment.

Similarly based on the patient's advanced directives and expectations(received by tool 22 as input data factors and patient data), thetreating team can adjust the output and change the threshold ofacceptable outcome. Accordingly, the output results may be based onthreshold values for treatment that may be configured by different carefacilities. For example, the output may adjust from ‘likelihood of agood outcome’ to ‘likelihood of a very good outcome’ based on theupdated threshold values or ranges.

The tool 22 may provide output results that can create a probabilisticmodel of a scale from very good outcome to bad outcome based on thevariables or treatment threshold values that would happen after thedecision making (e.g. as feedback). Example variables include:

-   -   Time to reperfusion    -   Quality of reperfusion    -   Unexpected medical events e.g. Hypotension    -   Complications of procedure    -   Complications during recovery e.g. pneumonia

The variables may be provided as part of a visual representation fordecision support. For example, green may represent good output and redmay represent bad output. The visual representation may dynamicallyadjust as new weighting factors are defined (e.g. using differentvalues) and variables are updated for different input factors. Thisprovides improved decision support as feedback from initial outputresults may trigger dynamic adjustment of the output to show new visualrepresentations for decision support. The revised output may provide anindication of the importance or relevance of different input variablesand weighting factors. This feedback loop may continue to update theoutput results dynamically to provide improved decision support.

The embodiments of the devices, systems and methods described herein maybe implemented in a combination of both hardware and software. Theseembodiments may be implemented on programmable computers, each computerincluding at least one processor, a data storage system (includingvolatile memory or non-volatile memory or other data storage elements ora combination thereof), and at least one communication interface.

Program code is applied to input data to perform the functions describedherein and to generate output information. The output information isapplied to one or more output devices. In some embodiments, thecommunication interface may be a network communication interface. Inembodiments in which elements may be combined, the communicationinterface may be a software communication interface, such as those forinter-process communication. In still other embodiments, there may be acombination of communication interfaces implemented as hardware,software, and combination thereof.

The hardware may include servers, services, interfaces, portals,platforms, or other systems formed from computing devices. It should beappreciated that the use of such terms is deemed to represent one ormore computing devices having at least one processor configured toexecute software instructions stored on a computer readable tangible,non-transitory medium. For example, a server can include one or morecomputers operating as a web server, database server, or other type ofcomputer server in a manner to fulfill described roles,responsibilities, or functions. The term “connected” or “coupled to” mayinclude both direct coupling (in which two elements that are coupled toeach other contact each other) and indirect coupling (in which at leastone additional element is located between the two elements).

The technical solution of embodiments may be in the form of a softwareproduct. The software product may be stored in a non-volatile ornon-transitory storage medium, which can be a compact disk read-onlymemory (CD-ROM), a USB flash disk, or a removable hard disk. Thesoftware product includes a number of instructions that enable acomputer device (personal computer, server, or network device) toexecute the methods provided by the embodiments.

The embodiments described herein are implemented by physical computerhardware, including computing devices, servers, receivers, transmitters,processors, memory, displays, and networks. The embodiments describedherein provide useful physical machines and particularly configuredcomputer hardware arrangements. The embodiments described herein aredirected to electronic machines and methods implemented by electronicmachines adapted for processing and transforming electromagnetic signalswhich represent various types of information.

FIG. 16 is a schematic diagram of the triage tool 22 according to someembodiments.

As depicted, the triage tool 22 includes at least one processor 220, atleast one memory unit or data storage device 222, at least one I/Ointerface 224, and at least one network interface 226.

Each processor 220 may be, for example, any type of general-purposemicroprocessor or microcontroller, a digital signal processing (DSP)processor, an integrated circuit, a field programmable gate array(FPGA), a reconfigurable processor, a programmable read-only memory(PROM), or any combination thereof. The processor may be configured toprocess input data (imaging and clinical factors) to provide outputresults as described herein.

Memory 222 may include a suitable combination of any type of computermemory that is located either internally or externally such as, forexample, random-access memory (RAM), read-only memory (ROM), compactdisc read-only memory (CDROM), electro-optical memory, magneto-opticalmemory, erasable programmable read-only memory (EPROM), andelectrically-erasable programmable read-only memory (EEPROM),Ferroelectric RAM (FRAM) or the like. The memory may store weightingfactors and input data factors that may be updated based on electronicsignals received from I/O interface 224.

Each I/O interface 224 enables the triage tool 22 to interconnect withone or more input devices, such as an imaging device, external memoryunit, keyboard, mouse, camera, touch screen and a microphone, or withone or more output devices such as a display screen and a speaker. TheI/O interface 224 may provide output results and receive feedback onoutput results. The interface 224 may connect to an imaging device suchas picture archiving and communication system (PACS) for storage andaccess to medical images from multiple modalities and source machinetypes. The imaging device may provide local storage, remote cloud basedstorage, or a combination thereof. Electronic images and reports may bestored and transmitted digitally via imaging device. The universalformat for PACS image storage and transfer is Digital Imaging andCommunications in Medicine (DICOM). The imaging device may include oneor more imaging modalities such as CT and MR and a secured network forthe transmission of patient and image data.

Each network interface 226 enables the triage tool 22 to communicatewith other components, to exchange data with other components, to accessand connect to network resources, to serve applications, and performother computing applications by connecting to a network (or multiplenetworks) capable of carrying data. The triage tool 22 may transmitoutput results via network interface 226 and may receive imaging datavia network interface 226, for example. The network interface 226 mayprovide output results and receive feedback on output results, asdescribed herein. This enables the tool 22 to integrated with variousinput devices and output devices that may be remote or local to tool 22.The network interface 226 may detect different imaging technologies toadapt tool 22 to interface therewith. For example, network interface 226may implement different drivers to connect with different imagingmodalities.

The triage tool 22 is operable to register and authenticate users (usinga login, unique identifier, and password for example) prior to providingaccess to applications, a local network, network resources, othernetworks and network security devices. The triage tool 22 may serve oneuser or multiple users.

FIG. 3A is a screenshot of a Computed Tomography Perfusion (CTP) mapidentifying the presence of a permeable thrombus of an interface thatmay be displayed on display device 102 as an example visualrepresentation of the output data. The visual representation providesCTP T0 maps identifying the presence of a permeable thrombus. A completeocclusion on CTA is shown at image 30 using a white arrow. Regions ofinterest (ROI) at the proximal thrombus interface are shown image 32using a solid white arrow and distal thrombus interface are shown atimage 32 using a hollow white arrow. The interfaces of the thrombus areshown as visual representations on the CTP average map in image 32. Aline profile (white arrow head) is drawn along the silhouette of theartery distal to the thrombus on the CTP average map. The CTP averagemap co-registered with the CTP T₀ map (image 34). A graph 36 plots T₀values against distance (pixel number) along the line profile are thenplotted and the line of best-fit determined.

FIG. 3B is a screenshot of a CTP map that may be displayed on displaydevice 102 as another example visual representation of the output data.The screenshot for this patient may identify the presence of a negativeartery profile slope (graph 44) suggests presence of retrograde flowdistal to thrombus. Other visual representations are shown by images 38,40, 42.

FIG. 4 provides graphs 40, 42, 44, 46 of recanalization rates. Earlyrecanalization rates with intravenous tPA stratified by differentimaging parameters may be measured using CTP T₀ maps. An image 40 showsearly recanalization rates in patients with positive slope (occultanterograde flow) as compared to negative slope (retrograde flow) arteryprofile distal to thrombus. An image 42 shows estimates of earlyrecanalization by T₀ value at distal thrombus interface. An image 44shows estimates of early recanalization by difference in T₀ valuebetween distal and proximal thrombus interface. An image 46 shows earlyrecanalization rates within the three groups of patients stratified bythe imaging parameters.

FIG. 5 is an example a table 50 for a multivariable logistics regressionmodel. The table shows multivariable logistic regression modeldetermining variables associated with early recanalization afterintravenous tPA thrombolysis. Group 1 relates to retrograde flow byArtery Profile where T₀ value difference between distal and proximalthrombus interface ROI>2 seconds may be the reference group Group 2relates to retrograde flow by Line Profile OR T₀ value differencebetween distal and proximal thrombus interface ROI>2 seconds. Group 3relates to anterograde flow by Line Profile and T₀ value differencebetween distal and proximal thrombus interface ROI<=2 seconds.

FIG. 6 is a screenshot of a visual representation of patient collateralswhich may be determined by the tool 22 using the imaging data asdescribed herein. The visual representation shows a patient with goodcollaterals, intermediate collaterals and poor collaterals of aninterface that may be displayed on display device 102. The upper panel60 shows a patient with a left M1 MCA occlusion (white arrow) and goodcollaterals (backfilling arteries) on multi-phase CTA. The middle panel62 shows a patient with a left M1 MCA occlusion (arrow) and intermediatecollaterals. Lower panel 64 shows a patient with a right M1 MCAocclusion (arrow) and poor collaterals (minimal backfilling arteries) onmulti-phase CTA. The interface may receive display screen specificationsand re-configure the display of the visual representations in variouspanels based on the display screen specifications. The panelconfiguration may be dynamically updated based on requested outputresults and the display screen specifications as there may be a limiteddisplay screen size and a variety of optional output results fordecision support.

FIG. 7 is a screenshot of visual representations of image slices frommulti-modal imaging. Multi-modal CT imaging at 2 hrs 51 mins postsymptom onset with NIHSS of 20 and right hemispherical symptoms.Non-contrast CT shows movement artefact; (panel 70). A proximal right M1MCA occlusion is seen (panel 72 with reference B-i). The visualrepresentation may relate to mCTA (with three phases) where maximumintensity projections are shown in panel 72 at references B-ii, iii andiv. Collateral circulation is modest with delay of two phases and someregions indicating minimal filling when compared to contralateral side.Perfusion CT T_(max) and CBF maps are depicted in panel 74 at referencesCi and ii. CTA and Perfusion CT imaging are congruent for assessment ofcollateral circulation beyond the occlusion. MR-diffusion imaging at 24hrs post admission imaging shows the final infarct as hyper intense(panel 76).

FIG. 8 is a screenshot of visual representations of image slices fromautomatic generation of aerial input functions for use in CT Perfusion.The upper panel 80 shows arterial voxels identified by a k-meansclassifier based on the area under curve (AUC) of the pixel time-densitycurve. The lower panel 82 shows a connected 4-voxel artery region (inthis case it is a 2×2 voxel region shown in outline) which has thehighest AUC among all similar TDCs from the arterial voxels (shown inoutline) in this slice as aerial input functions.

FIG. 9 illustrates visual representations of time-based CT Perfusionthresholds charts 90, 92, 94 and a brain view image representing anexample of time-based CT Perfusion thresholds that helps estimate futurebrain infarct over given time data for CTP. The visual representationillustrates charts representing data for CTP to reperfusion. Charts 90,92, 94 show that the CTP-T_(max) and CBF patient-level thresholds topredict infarction are correlated with the time from CTP-to-reperfusion.The brain view image depicts CTP optimal thresholds for infarction basedon time-to-reperfusion for all patients combined (total voxel-by-voxelanalysis). The brain view image shows three example visual indications96, 97, 98 for different values for T_(max). A visual indication 96relates to T_(max) greater than 16 seconds and CBF less than 0.20. Avisual indication 97 relates to T_(max) greater than 12.5 seconds andCBF less than 0.30 A visual indication 98 relates to T_(max) greaterthan 9.5 seconds.

FIG. 10 illustrates a visual representation of an example time basedmodel for infarct growth using CT Perfusion according to someembodiments with different visual representations 1020, 1040, 1060 fordifferent values for T_(max) and CBF.

FIG. 11 is a screen shot of a visual representation of an image slice ofa CTP study according to some embodiments that demonstrates techniquesfor patient motion correction. This may result from a process to removeunacceptable images for CTP analysis due to motion according to someembodiments. Examples of patient motion are shown in FIGS. 12 and 13.The interface may be displayed on display device. This may be generatedusing an automated method for removal of z-axis motion correction.

A panel 1100 shows automatic generation of whole brain region ofinterest in a slice after removal of skull. A panel 1102 shows a timedensity curve (TDC) of the whole brain region shown in panel 1100 afterbaseline subtraction and normalization by the average value of thesubtracted curve. In order to be displayed together with theautomatically detected arterial input function (FIG. 8), the normalizedwhole brain TDC has been scaled up by a factor of 100. A panel 1104shows the smoothed fitted curve to the normalized whole brain TDC wasfound by deconvolution with the arterial input function. A panel 1106shows the absolute difference between the normalized whole brain TDC andthe fitted curve. The images may have significant z-axis movementrelative to the rest of the images, for example, as shown by thedifferences of the skull representations.

FIG. 12 is a screen shot of a visual representation of image slices of aCTP study that shows patient motion in the Z-axis. according to someembodiments. Z-axis motion of the images of a slice from a CT Perfusionstudy. (A) The first image of the slice at time 0 sec. (B) Image at 2.8sec. (C) Image at 36.4 sec. (D) Image at 104.0 sec. Motion led todifferences in the skull within the dotted circles.

FIG. 13 is a screen shot of a visual representation of image slices of aCTP study showing the effect of z-axis motion on perfusion parametermaps of a CT Perfusion study according to some embodiments. Theinterface may be displayed on a display device. Effect of z-axis motionon perfusion parameter maps of a CT Perfusion Study. The CBF and T_(max)maps with and without z-axis motion correction are shown together withthe mean value within a circular region of interest within the strokeaffected hemisphere and contralateral hemisphere. Panels 1300, 1302 showa CBF map without and with z-axis motion correction respectivelydisplayed in the scale from 0-120 mL·min⁻¹. (100 g)⁻¹. Panels 1304, 1306show T_(max) map without and with z-axis motion correction respectivelydisplayed in the scale from 0-16 seconds. The pixel values of theT_(max) maps have been scaled up by a factor of 100 to facilitate thedisplay of the maps, according to some embodiments. This may be screenshot of the functional maps from the same CTP study as FIG. 12 showingthe effect with and without correction of head motion, for example.

FIG. 14 is a screen shot of visual representations of image slices froman application of time based infarct growth according to someembodiments. The visual representation illustrates an applied automatedtime based infarct growth paradigm on to perfusion maps and consequentlyvalidating them that may be displayed on an interface that may bedisplayed on display device 102. The screenshots may be generated byapplying the automated time based infarct growth paradigm on toperfusion maps and consequently validating them. A panel 1400 shows abrain image with gray-matter segmentation and a panel 1402 shows anotherbrain image with clustering to remove noise. The tool 22 may implementclustering techniques to provide an improved visual representation. Apanel 1404 may show a “time is brain” paradigm to illustrate rates ofirreversible infarct over time based on T_(max), CBF and CBV values.

FIG. 15 is a screen shot of a visual representation of an example of a3D clot segmentation 1500 from non-contrast CT representation (cornerpanel 1502) using proposed automated technique.

FIGS. 17 to 21 are schematics of example systems with the triage toolaccording to some embodiments.

FIG. 17 shows a system with a decision support tool 22 according to someembodiments. The example system includes the triage tool 22, an imagedata store 108, a display controller 106. The tool 22 receives brainscan or imaging data from an imaging device 104. Alternatively, thebrain scan data may be received at data store 108 for storage andsubsequent retrieval or access by tool 22. The display controller 106control output of visual representations on a display 102.

For simplicity only one tool 22 is shown but system may include moretool 22 operable by users to access remote network resources andexchange data. The tool 22 may be the same or different types ofdevices. The tool 22 includes at least one processor, a data storagedevice (including volatile memory or non-volatile memory or other datastorage elements or a combination thereof), and at least onecommunication interface (an example of which is shown in FIG. 16). Thetool 22 components may be connected in various ways including directlycoupled, indirectly coupled via a network, and distributed over a widegeographic area and connected via a network (which may be referred to as“cloud computing”).

For example, and without limitation, the tool 22 may be a server,network appliance, set-top box, embedded device, computer expansionmodule, personal computer, laptop, personal data assistant, cellulartelephone, smartphone device, UMPC tablets, video display terminal, andwireless hypermedia device or any other computing device capable ofbeing configured to carry out the methods described herein.

The imaging device 104 may be a PACS for storage and access to medicalimages from multiple modalities and source machine types. The imagingdevice 104 may provide local storage, remote cloud based storage, or acombination thereof. Electronic images and reports may be stored andtransmitted digitally via imaging device. The universal format for PACSimage storage and transfer is DICOM. Further, imaging device 104 maymanage non-image data, such as scanned documents. The imaging device 104may include one or more imaging modalities such as CT and MR and asecured network for the transmission of patient and image data. Theimaging device 104 may also workstations for interpreting and reviewingimages and archives for the storage and retrieval of images and reports.Image device 104 may provide one or more of image creation, retrieval,distribution, and display.

The display controller 106 may receive configuration parameters tocontrol the display and provision of the visual representation on thedisplay. For example, the configuration parameters may receive a selectset of output data to use for generation of the visual representation.The configuration parameters may include details regarding the displaydevice and its capabilities. The display controller 106 may receiveinput from display 102 to reconfigure and update the rendering of thevisual representations. The interface may include selectable indicia forreceiving updates to configuration parameters for provisional to thedisplay controller 106. The display controller 106 may provide anyreceived configuration parameters to triage tool 22 as feedback toupdate the generation of output results, for example. Accordingly, thedisplay controller 106 facilitates acquisition of feedback data and isinvolved in updating the visual representation based on the updatedoutput results from the feedback. This facilitates the feedback loop asa visual representation may effectively illustrate the revised outputand the impact of the feedback on the output.

FIG. 18 is another example system with triage tool 22. In this examplesystem, the triage tool 22 may be integrated as part of the imagingdevice 104 to process scans or images captured and generated by theimaging device 104 and stored in image data store 108. In this examplesystem, the triage tool 22 may also be integrated as part of the displaydevice 102 to display output and visual representations of the treatmentprotocol. The integrated interface between tool 22 and imaging device104 may enable imaging modality specific configurations to beincorporated into tool 22 for improved processing.

FIG. 19 is another example system with triage tool 22. In this examplesystem, the triage tool 22 may be integrated as part of the imagingdevice 104 to process scans or images captured and generated by theimaging device 104 and stored in image data store 108. The display 102may be a separate add on. This illustrates the versatility of tool 22and the various system configurations it supports.

FIG. 20 is another example system with triage tool 22. In this examplesystem, the triage tool 22 may be integrated as part of the displaydevice 102 to display output data including visual representations of atreatment protocol, where the display controller 106 interfaces betweenthe triage tool 22 and the display device 102. Although only one imagingdevice 104 is shown, tool 22 may integrate with multiple imaging devices104 of different modalities. An interface may configure multipleconnections to the different imaging devices 104.

FIG. 21 is a schematic diagram of another system with triage tool 22exemplary of an embodiment. In this example, the triage tool 22 connectsto imaging device 104 via a network 110. The network 110 may include theInternet, Ethernet, plain old telephone service (POTS) line, publicswitch telephone network (PSTN), integrated services digital network(ISDN), digital subscriber line (DSL), coaxial cable, fiber optics,satellite, mobile, wireless (e.g. WiMAX), SS7 signaling network, fixedline, local area network, wide area network, and others, including anycombination of these. The triage tool 22 may receive imaging data fromimaging device 104 via network 110, for example. The triage tool 22 mayprovide feedback and control commands to imaging device 104 via network110. The triage tool 22 may transmit output results via network 110 to adisplay device or another processor for further data analysis or as anotification message. The network 110 may include PACS as describedherein to access images.

The triage tool 22 may connect to a health care provider device 114configured to display output results in an interface and receive controlcommands and feedback via the interface. The health care provider device114 may be a workstation or a mobile device for example, to facilitateremote access of output results by health care provider. The triage tool22 may connect to a central server 112 implementing quality controlprocesses to validate data, receive feedback from different tools 22,and output results. Accordingly, a central server 112 may facilitatecoordination of data and refinements across multiple tools 22.

The foregoing discussion provides many example embodiments. Althougheach embodiment represents a single combination of inventive elements,the inventive subject matter is considered to include all possiblecombinations of the disclosed elements. Thus if one embodiment compriseselements A, B, and C, and a second embodiment comprises elements B andD, then the inventive subject matter is also considered to include otherremaining combinations of A, B, C, or D, even if not explicitlydisclosed.

Although the present invention has been described and illustrated withrespect to preferred embodiments and preferred uses thereof, it is notto be so limited since modifications and changes can be made thereinwhich are within the full, intended scope of the invention as understoodby those skilled in the art.

1. A method for a decision support tool for evaluating a patientsuffering from acute stroke, comprising: receiving patient clinicalinformation and patient brain scan electronic images at a processor;generating, at the processor, a patient brain imaging profile using thepatient clinical information and the brain scan electronic images, theimaging profile identifying a quantity and eloquence of brain tissuethat is irreversibly infarcted, an estimated rate or quantity of patientbrain tissue that will become irreversibly infarcted at a future timebased, a thrombus morphology associated with an estimate of a thrombusdissolving at the future time, and an estimated collateral blood flow;determining an estimated transport time to transfer the patient to atreatment facility and an estimated treatment time for receivingreperfusion at the treatment facility; dynamically determining, usingthe processor, a patient assessment profile by: processing the patientclinical information, the patient brain imaging profile, the estimatedtransport time, and the estimated treatment time to generate input datavalues; dynamically deriving weighting factors as an assessment ofimportance or relevance of the input data values and assigning theweighting factors to the input data values; deriving as output datavalues for the patient assessment profile using the input data valuesand the weighting factors, the output data values being a probability ofan expert treatment decision for transferring the patient to thetreatment facility and providing the reperfusion at the treatmentfacility, and a visual representation of the thrombus morphology, theestimated collateral blood flow, and an estimated quantity of braintissue that will likely become irreversibly infarcted after theestimated transport time and/or the estimated treatment time; outputtingthe output values as clinical decision support information to triggerdisplay on a display device, storage on a storage device, ortransmission to another processor using a transmitter.
 2. The method ofclaim 1 further comprising: determining that the patient is already atthe treatment facility and updating the visual representation with theestimated quantity of brain tissue that will likely become irreversiblyinfarcted after the estimated treatment time for accomplishingreperfusion.
 3. The method of claim 1 further comprising: determining orreceiving a patient clinical data profile identifying an age or agerange for the patient and a stroke severity, the stroke severity definedon a scale of mild, moderate and severe or based on physicianheuristics, and determining the patient assessment profile using thepatient clinical data profile as input.
 4. The method in claim 1 furthercomprising determining one or more of: the time elapsed since the onsetof stroke symptoms as an additional input data values for the patientassessment profile; the patient's pre-morbid status, general health andco-morbidities as an additional input data values for the patientassessment profile; the patient's advanced directives as an additionalinput data values for the patient assessment profile; and currentmedications and/or medical history of patient that significantlyinfluence decision making as an additional input data values for thepatient assessment profile, including blood thinners and recent surgery.5. The method of claim 1 further comprising providing an imaginginterface to connect to an imaging device to receive the brain scanimage files, the imaging device selected from the group consisting of ascanner, a picture archiving communication system network, and a cloudimage storage device, and wherein the patient brain electronic imagesmay be of one or more imaging modalities selected from the groupconsisting of CT scan, multi-phase CTA, and CT perfusion, MRI, TCD US,EIS, and other imaging modalities.
 6. The method of claim 1 whereindetermining the estimated transport time and the estimated treatmenttime comprises determining a required treatment for the patient andidentifying one or more available treatment facilities based onavailable treatment services and equipment, available treatment times,available transportation type and the required treatment of the patient.7. The method of claim 1 further comprising continuously updating thepatient assessment profile using a feedback loop based on additionalinput data values including configurations for the current physician andhealth system, additional available patient and health system data,changing configurations for the physician and health care facility,updates for the one or more weighting factors, or control commandsreceived from a display device displaying the visual representation. 8.The method of claim 1 further comprising constructing and continuouslyvalidating the patient assessment profile and the input data valuesusing current and future clinical trial datasets.
 9. The method of claim1 further comprising constructing and continuously validating thepatient assessment profile by receiving additional data and results onadjuvant therapies including neuro-protection and augmented thrombolytictechniques to change physician and health system heuristics.
 10. Themethod of claim 1 further comprising receiving threshold data for ahealth care provider to update and customize the patient assessmentprofile, the weighting factors, and the input data values for the healthcare provider, the health care data including number of treatmentcenters providing endovascular treatment, staff availability, and othercurrent health care metrics.
 11. The method of claim 1, whereindetermining the patient assessment profile further comprises determininga rate of brain tissue death using collateral assessment on CTA, CTPerfusion, MRI, TDC, US, EIS or other brain and neurovascular imagingmodality or a combination of thereof.
 12. The method of claim 1, whereinthe likelihood of the thrombus dissolving the over future time isdetermined by one or more techniques of measuring thrombus morphologysuch as a size of the thrombus, length of the thrombus, surface area ofthe thrombus, volume of the thrombus, and permeability to blood flow ofthe thrombus.
 13. The method of claim 1 further comprising determining alikelihood of the thrombus dissolving with administration of athrombolytic drug using the thrombus morphology and the collateral bloodflow, the patient treatment protocol indicating the likelihood of thethrombus dissolving with administration of the thrombolytic drug. 14.The method of claim 1 wherein the output data values of the patientassessment profile indicates a comparison between risks of theadministration of a thrombolytic drug and risks of endovasculartreatment, the risks including a bleeding risk and other potentiallymajor risks associated with thrombolytic drug administration and atreatment risk of not being able to administer the endovasculartreatment or not successfully providing the endovascular treatment. 15.The method of claim 1 wherein the collateral blood flow is determinedusing mCTA, T₀ and T_(max) values.
 16. The method of claim 1 wherein thepatient treatment protocol is selected from the group consisting of:transferring the patient to the treatment facility for treatment withendovascular therapy; transferring the patient to the treatment facilityfor direct treatment without additional or repeating brain scans;retaining the patient at an initial treatment facility for treatmentwith a thrombolytic drug; and retaining the patient at the initialtreatment facility.
 17. The method of claim 1 further comprising:receiving additional patient, clinical and imaging data for strokepatients; updating the input data values using the additional patient,clinical and imaging data for stroke patients; and updating patienttreatment protocol using machine learning and the additional patientdata, health system data, the updating by applying additional weightingfactors to the updated input data values.
 18. The method of claim 1wherein the treatment protocol indicates one or more of an automatedprediction of thrombus lysability using the thrombus morphology, anautomated quantitation of collateral status on a CTP map and onmulti-phase CTA and an automated assessment of severe hypoattenuation onnon-contrast CT.
 19. A decision support computing tool comprising: animage interface to receive patient brain electronic images; a processorto: receive patient clinical information; generate a patient brainimaging profile using the patient brain scan electronic images and thepatient clinical information, the imaging profile identifying a quantityand eloquence of brain tissue that is irreversibly infarcted, anestimated rate or quantity of patient brain tissue that will becomeirreversibly infarcted at a future time, a thrombus morphologyassociated with an estimate of a thrombus dissolving at the future time,and an estimated collateral blood flow; determine an estimated transporttime to transfer the patient to a treatment facility and an estimatedtreatment time for receiving reperfusion at the treatment facility; anddynamically determining a patient assessment profile by: processing thepatient clinical information, the patient brain imaging profile, theestimated transport time, and the estimated treatment time to generateinput data values; dynamically deriving weighting factors as anassessment of importance or relevance of the input data values andassigning the weighting factors to the input data values; derivingoutput data values for the patient assessment profile using the inputdata values and the weighting factors, the output data values being aprobability of an expert treatment decision for transferring the patientto the treatment facility and providing the reperfusion at the treatmentfacility, and a visual representation of the thrombus morphology, theestimated collateral blood flow, and an estimated quantity of braintissue that will likely become irreversibly infarcted after theestimated transport time and/or the estimated treatment time; and adisplay device to display the output data values as clinical decisionsupport information including the visual representation; and a networkinterface to provide the output data values to trigger transmission orstorage.
 20. An imaging system for evaluating a patient suffering fromacute stroke, comprising: an imaging system to receive patient brainelectronic images; a decision support computing tool with a processorto: receive patient clinical information; generate a patient brainimaging profile using the patient brain scan electronic images and thepatient clinical information, the imaging profile identifying a quantityand eloquence of brain tissue that is irreversibly infarcted, anestimated rate or quantity of patient brain tissue that likely willbecome irreversibly infarcted at a future time, a thrombus morphologyassociated with an estimate of a thrombus dissolving at the future time,and an estimated collateral blood flow; determine an estimated transporttime to transfer the patient to a treatment facility and an estimatedtreatment time for receiving reperfusion at the treatment facility; anddynamically determining a patient assessment profile by: processing thepatient clinical information, the patient brain imaging profile, theestimated transport time, and the estimated treatment time to generateinput data values; dynamically deriving weighting factors as anassessment of importance or relevance of the input data values andassigning the weighting factors to the input data values; deriving asoutput data values for the patient assessment profile using the inputdata values and the weighting factors, the output data values being aprobability of an expert treatment decision for transferring the patientto the treatment facility and providing the reperfusion at the treatmentfacility, and a visual representation of the thrombus morphology, theestimated collateral blood flow, and an estimated quantity of braintissue that will likely become irreversibly infarcted after theestimated transport time and/or the estimated treatment time; an outputdevice to output the output data results as clinical decision supportinformation to trigger display of the output data results on a displaydevice, storage in a data storage device, or transmission for atransmitter.